Author: "Kovari H" / Topic: 10234 clinic for infectious diseases - Searchworks@Jio Institute Digital Library Search Results

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1. Changes in alanine aminotransferase levels after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in HIV-positive people without viral hepatitis in the Swiss HIV Cohort Study

Author: Kovari, H, Surial, B, Tarr, P E, Cavassini, M, Calmy, A, Schmid, P, Bernasconi, E, Rauch, A, Wandeler, G, Ledergerber, B, Swiss HIV Cohort Study, University of Zurich, and Kovari, H
Subjects: 10234 Clinic for Infectious Diseases, 2736 Pharmacology (medical), 610 Medicine & health, 2725 Infectious Diseases, 2719 Health Policy
Published: 2021

2. Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D study

Author: Hatleberg, Ci, Ryom, L, El-Sadr, W, Mocroft, A, Reiss, P, De Wit, S, Dabis, F, Pradier, C, d'Arminio Monforte, A, Kovari, H, Law, M, Lundgren, Jd, Sabin, Ca, Data Collection of Adverse Events of Anti-HIV drugs (D:A:D) Study group, Calvo, G, Bonnet, F, Kirk, O, Morfeldt, L, Weber, R, Lind-Thomsen, A, Salbøl Brandt, R, Hillebreght, M, Zaheri, S, Wit, F, Scherrer, A, Schöni-Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Le Marec, F, Boerg, E, Thulin, E, Sundström, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Mateu, S, Torres, F, Petoumenos, K, Blance, A, Huang, R, Puhr, R, Laut, K, Kristensen, D, Phillips, An, Kamara, Da, Smith, Cj, Brandt, Rs, Raben, D, Matthews, C, Bojesen, A, Grevsen, Al, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Smit, C, Ross, M, Fux, Ca, Morlat, P, Friis-Møller, N, Kowalska, J, Bohlius, J, Bower, M, Fätkenheuer, G, Grulich, A, Sjøl, A, Meidahl, P, Iversen, Js, Hillebregt, M, Prins, Jm, Kuijpers, Tw, Scherpbier, Hj, van der Meer, J, Godfried, Mh, van der Poll, T, Nellen, F, Geerlings, Se, van Vugt, M, Pajkrt, D, Bos, Jc, Wiersinga, Wj, van der Valk, M, Goorhuis, A, Hovius, Jw, van Eden, J, Henderiks, A, van Hes, A, Mutschelknauss, M, Nobel, He, Pijnappel, F, Jurriaans, S, Back, N, Zaaijer, Hl, Berkhout, B, Cornelissen, M, Schinkel, Cj, Thomas, Xv, De Ruyter Ziekenhuis, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Ziekenhuis, C, Pronk, M, Ammerlaan, H, de Munnik, E, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, Weijsenfeld, Am, van der Ende ME, van Gorp, E, Schurink, C, Nouwen, Jl, Verbon, A, Rijnders, B, Bax, Hi, van der Feltz, M, van der Bassant, N, van Beek, J, Vriesde, M, van Zonneveld LM, de Oude-Lubbers, A, van den Berg-Cameron HJ, Bruinsma-Broekman, Fb, de Groot, J, de Zeeuw-de Man, M, Boucher, C, Koopmans, M, van Kampen, J, Pas, Sd, Driessen, G, van Rossum, A, van der Knaap LC, Flevoziekenhuis, E, Branger, J, Rijkeboer-Mes, A, Schippers, Ef, van IJperen JM, Geilings, J, van der Hut, G, Franck, P, van Eeden, A, Brokking, W, Groot, M, Elsenburg, L, Damen, M, Isala, Is, Groeneveld, P, Bouwhuis, Jw, den Berg JF, van Hulzen, A, van der Bliek GL, Bor, P, Bloembergen, P, Wolfhagen, M, Ruijs, G, Kroon, Fp, de Boer, M, Bauer, Mp, Jolink, H, Vollaard, Am, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander JG, Pogany, K, Roukens, A, Kastelijns, M, Smit, Jv, Smit, E, Struik-Kalkman, D, Tearno, C, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, Sh, Oude Lashof, A, Posthouwer, D, Ackens, Rp, Schippers, J, Vergoossen, R, Weijenberg-Maes, B, van Loo, I, Havenith, T, Leyten, E, Gelinck, L, van Hartingsveld, A, Meerkerk, C, Wildenbeest, Gs, Mutsaers, J, Jansen, Cl, Mulder, Jw, Vrouenraets, S, Lauw, Fn, van Broekhuizen MC, Paap, H, Vlasblom, Dj, Smits, P, Weijer, S, El Moussaoui, R, Bosma, As, van Vonderen, M, van Houte, D, Kampschreur, Lm, Dijkstra, K, Faber, S, Weel, J, Kootstra, Gj, Delsing, Ce, van der Burg-van de Plas, M, Heins, H, Lucas, E, Kortmann, W, van Twillert, G, Cohen Stuart, J, Diederen, B, Pronk, D, van Truijen-Oud FA, van der Reijden WA, Jansen, R, Brinkman, K, den Berk, G, Blok, Wl, Frissen, P, Lettinga, Kd, Schouten, W, Veenstra, J, Brouwer, Cj, Geerders, Gf, Hoeksema, K, Kleene, Mj, van der Meché IB, Spelbrink, M, Sulman, H, Toonen, A, Wijnands, S, Kwa, D, Witte, E, Koopmans, Pp, Keuter, M, van der Ven, A, Ter Hofstede, H, Dofferhoff, A, van Crevel, R, Albers, M, Bosch, M, Grintjes-Huisman, K, Zomer, Bj, Stelma, Ff, Rahamat-Langendoen, J, Burger, D, Richter, C, Gisolf, Eh, Hassing, Rj, Ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, Hulshoff, N, van der Prijt, L, van der Swaluw, J, Bermon, N, Herpers, Bl, Veenendaal, D, Verhagen, D, van Wijk, M, Brouwer, Ae, Kuipers, M, Santegoets, R, van der Ven, B, Marcelis, Jh, Buiting, A, Kabel, Pj, Bierman, W, Scholvinck, H, Wilting, Kr, Stienstra, Y, van der Meulen PA, de Weerd DA, Ludwig-Roukema, J, Niesters, H, Riezebos-Brilman, A, van Leer-Buter CC, Knoester, M, Hoepelman, A, Mudrikova, T, Ellerbroek, Pm, Oosterheert, Jj, Arends, Je, Barth, Re, Wassenberg, M, Schadd, Em, van Elst-Laurijssen, D, van Oers-Hazelzet, E, Vervoort, S, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Peters, E, van Agtmael MA, Bomers, M, de Vocht, J, Heitmuller, M, Laan, Lm, Pettersson, Am, Ang, Cw, Geelen, S, Wolfs, T, Bont, Lj, Bezemer, Do, van Sighem AI, Boender, Ts, de Jong, A, Bergsma, D, Hoekstra, P, de Lang, A, Grivell, S, Jansen, A, Rademaker, Mj, Raethke, M, Meijering, R, Schnörr, S, de Groot, L, van den Akker, M, Bakker, Y, Claessen, E, El Berkaoui, A, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, van de Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, van der Vliet, S, Wisse, A, Woudstra, T, Tuk, B, Dupon, M, Gaborieau, V, Lacoste, D, Malvy, D, Mercié, P, Neau, D, Pellegrin, Jl, Tchamgoué, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, Mo, Gérard, Y, Blanco, P, Bouchet, S, Breilh, D, Fleury, H, Pellegrin, I, Chêne, G, Thiébaut, R, Wittkop, L, Lawson-Ayayi, S, Gimbert, A, Desjardin, S, Lacaze-Buzy, L, Petrov-Sanchez, V, André, K, Bernard, N, Caubet, O, Caunegre, L, Chossat, I, Courtault, C, Dauchy, Fa, Dondia, D, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Ferrand, H, Gerard, Y, Greib, C, Hessamfar, M, Imbert, Y, Lataste, P, Marie, J, Mechain, M, Monlun, E, Ochoa, A, Pistone, T, Raymond, I, Receveur, Mc, Rispal, P, Sorin, L, Valette, C, Vandenhende, Ma, Viallard, Jf, Wille, H, Wirth, G, Lafon, Me, Trimoulet, P, Bellecave, P, Tumiotto, C, Haramburu, F, Miremeont-Salamé, G, Blaizeau, Mj, Decoin, M, Hannapier, C, Pougetoux, Elea, Delveaux, S, D'Ivernois, C, Diarra, F, Uwamaliya-Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Carr, A, Cooper, D, O'Sullivan, M, Nolan, D, Guelfi, G, Domingo, P, Sambeat, Ma, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, Clumeck, N, Gennotte, Af, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, Mc, Semaille, P, Van Laethem, Y, Neaton, J, Krum, E, Thompson, G, Luskin-Hawk, R, Telzak, E, Abrams, Di, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, Lr, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Losso, M, Pedersen, C, Ristola, M, Phillips, A, Rockstroh, J, Peters, L, Fischer, Ah, Grønborg Laut, K, Larsen, Jf, Podlekareva, D, Cozzi-Lepri, A, Shepherd, L, Schultze, A, Amele, S, Kundro, M, Schmied, B, Vassilenko, A, Mitsura, Vm, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Møller, Nf, Ostergaard, L, Wiese, L, Nielsen, Ln, Zilmer, K, Aho, I, Viard, Jp, Girard, Pm, Duvivier, C, Degen, O, Stellbrink, Hj, Stefan, C, Bogner, J, Chkhartishvili, N, Gargalianos, P, Szlávik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Elbirt, D, Sthoeger, Zm, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, Plazzi, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Staub, T, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, Aksak-Was, B, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Caldeira, L, Radoi, R, Panteleev, A, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Gatell, Jm, Miró, Jm, Moreno, S, Rodriguez, Jm, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, Jm, Falconer, K, Thalme, A, Sonnerborg, A, Blaxhult, A, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, Am, Simons, E, Johnson, Ma, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Thulin, G, Åkerlund, B, Koppel, K, Karlsson, A, Håkangård, C, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Marchetti, Gc, Perno, Cf, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, Mr, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marchetti, G, Marcotullio, S, Monno, L, Nozza, S, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, Mm, Saracino, A, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Santoro, C, Suardi, C, Donati, V, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, Pe, Piano, P, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Chiodera, A, Milini, P, Rizzardini, G, Moioli, Mc, Piolini, R, Ridolfo, Al, Salpietro, S, Tincati, C, Puzzolante, C, Abrescia, N, Chirianni, A, Borgia, G, Orlando, R, Bonadies, G, Di Martino, F, Gentile, I, Maddaloni, L, Cattelan, Am, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, Ma, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Fontanelli Sulekova, L, Iaiani, G, Latini, A, Mastrorosa, I, Plazzi, Mm, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Fontana Del Vecchio, R, Francisci, D, Di Giuli, C, Caramello, P, Orofino, Gc, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Dollet, K, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador-Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost-Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, Pm, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, Dl, Bucher, H, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Günthard, Hf, Haerry, D, Hasse, B, Hirsch, Hh, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, Rd, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Marzolini, C, Metzner, Kj, Müller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Scherrer, Au, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S., Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Global Health, Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Inflammatory diseases, AII - Amsterdam institute for Infection and Immunity, General Internal Medicine, APH - Quality of Care, Graduate School, Center of Experimental and Molecular Medicine, Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, ARD - Amsterdam Reproduction and Development, Hatleberg, Camilla I, Ryom, Lene, El-Sadr, Wafaa, Mocroft, Amanda, Reiss, Peter, De Wit, Stephane, Dabis, Francoi, Pradier, Christian, d'Arminio Monforte, Antonella, Kovari, Helen, Law, Matthew, Lundgren, Jens D, Sabin, Caroline A, Dad, Study, Castagna, A, Infektiosairauksien yksikkö, Department of Medicine, Clinicum, HUS Inflammation Center, HUS Internal Medicine and Rehabilitation, MUMC+: DA MMI AIOS (9), MUMC+: DA MMI Infectieserologie (9), Med Microbiol, Infect Dis & Infect Prev, MUMC+: DA MMI Staf (9), RS: FHML non-thematic output, and University of Zurich
Subjects: Male, Cardiovascular disease, gender, cardiovascular disease interventions, cohort studies, HIV, women, myocardial infarction, stroke, Heart disease, Psychological intervention, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030204 cardiovascular system & hematology, Santé publique, ACUTE CORONARY SYNDROME, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, Risk Factors, HIV Seropositivity, Medicine and Health Sciences, IN-HOSPITAL MORTALITY, 030212 general & internal medicine, Pathologie maladies infectieuses, Stroke, Research Articles, PRESENTATION, GENERAL-POPULATION, INFECTED PATIENTS, Sex Characteristics, Confounding, Middle Aged, 3. Good health, Infectious Diseases, Cardiovascular Diseases, Cardiovascular disease interventions, Cohort studies, Gender, Hiv, Myocardial infarction, Women, symbols, Female, Cohort study, Research Article, Adult, medicine.medical_specialty, Acute coronary syndrome, ACUTE MYOCARDIAL-INFARCTION, SEX-DIFFERENCES, SYMPTOM PRESENTATION, education, 610 Medicine & health, HEART-DISEASE, NO, INFECTED, 03 medical and health sciences, symbols.namesake, Internal medicine, cardiovascular disease intervention, PATIENTS, medicine, Humans, SYMPTOM, Poisson regression, IN-HOSPITAL, business.industry, MORTALITY, CLINICAL PRESENTATION, Public Health, Environmental and Occupational Health, 2739 Public Health, Environmental and Occupational Health, 2725 Infectious Diseases, medicine.disease, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 10036 Medical Clinic, 3121 General medicine, internal medicine and other clinical medicine, RISK-FACTORS, Observational study, business, cohort studie
Abstract: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV-positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study. Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders. Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti-hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow-up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti-hypertensives (1.17 [1.10, 1.25]). Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV-positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2018
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3. Origin of Minority Drug-Resistant HIV-1 Variants in Primary HIV-1 Infection

Author: Metzner, K. J., Scherrer, A. U., Preiswerk, B., Joos, B., von Wyl, V., Leemann, C., Rieder, P., Braun, D., Grube, C., Kuster, H., Boni, J., Yerly, S., Klimkait, T., Aubert, V., Furrer, H., Battegay, M., Vernazza, P. L., Cavassini, M., Calmy, A., Bernasconi, E., Weber, R., Gunthard, H. F., Barth, J., Bucher, H. C., Burton-Jeangros, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., University of Zurich, Metzner, Karin J, Swiss HIV Cohort Study, Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., and Trkola, A.
Subjects: Male, HIV Infections, Drug resistance, Polymerase Chain Reaction, law.invention, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, law, Adolescent, Adult, Aged, Alleles, Cluster Analysis, Drug Resistance, Viral, Female, Genetic Variation, HIV Infections/transmission, HIV Infections/virology, HIV-1/drug effects, HIV-1/genetics, Humans, Middle Aged, Phylogeny, Sequence Analysis, DNA, Switzerland, Young Adult, Immunology and Allergy, 030212 general & internal medicine, Young adult, 610 Medicine & health, Polymerase chain reaction, ddc:616, 0303 health sciences, biology, Transmission (medicine), Resistance mutation, 3. Good health, Integrase, Infectious Diseases, 2723 Immunology and Allergy, Peripheral blood mononuclear cell, 03 medical and health sciences, Allele, 030304 developmental biology, HIV-1/drug effects/genetics/isolation & purification, 2725 Infectious Diseases, HIV Infections/transmission/virology, Virology, Immunology, HIV-1, biology.protein
Abstract: Background. Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants (MVs) are present in some antiretroviral therapy (ART)–naive patients. They may result from de novo mutagenesis or transmission. To date, the latter has not been proven. Methods. MVs were quantified by allele-specific polymerase chain reaction in 204 acute or recent seroconverters from the Zurich Primary HIV Infection study and 382 ART-naive, chronically infected patients. Phylogenetic analyses identified transmission clusters. Results. Three lines of evidence were observed in support of transmission of MVs. First, potential transmitters were identified for 12 of 16 acute or recent seroconverters harboring M184V MVs. These variants were also detected in plasma and/or peripheral blood mononuclear cells at the estimated time of transmission in 3 of 4 potential transmitters who experienced virological failure accompanied by the selection of the M184V mutation before transmission. Second, prevalence between MVs harboring the frequent mutation M184V and the particularly uncommon integrase mutation N155H differed highly significantly in acute or recent seroconverters (8.2% vs 0.5%; P < .001). Third, the prevalence of less-fit M184V MVs is significantly higher in acutely or recently than in chronically HIV-1–infected patients (8.2% vs 2.5%; P = .004). Conclusions. Drug-resistant HIV-1 MVs can be transmitted. To what extent the origin—transmission vs sporadic appearance—of these variants determines their impact on ART needs to be further explored.
Published: 2013
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4. Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIRaben-1 subtype B and non-subtype B receiving a salvage regimen

Author: De Luca A., Flandre P., Dunn D., Zazzi M., Wensing A., Santoro M. M., Gunthard H. F., Wittkop L., Kordossis T., Garcia F., Castagna A., Cozzi-Lepri A., Churchill D., De Wit S., Brockmeyer N. H., Imaz A., Mussini C., Obel N., Perno C. F., Roca B., Reiss P., Schulter E., Torti C., van Sighem A., Zangerle R., Descamps D., Mocroft A., Kirk O., Sabin C., Casadi W., Casabona J., Miro J. M., Touloumi G., Garrido M., Teira R., Wit F., Warszawski J., Meyer L., Dabis F., Krause M. M., Ghosn J., Leport C., Prins M., Bucher H., Gibb D., Fatkenheuer G., del Amo J., Thorne C., Stephan C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., d'Arminio Monforte A., Prieto L., Conejo P. R., Soriano-Arandes A., Battegay M., Kouyos R., Tookey P., Konopnick D., Goetghebuer T., Sonnerborg A., Haerry D., de Wit S., Costagliola D., Raben D., Chene G., Ceccherini-Silberstein F., Gunthard H., Judd A., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Brandt R. S., Berenguer J., Bohlius J., Bouteloup V., Davies M. -A., Dorrucci M., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Schomaker M., Smit C., Sterne J., Thiebaut R., van der Valk M., Wyss N., Aubert V., Bernasconi E., Boni J., Burton-Jeangros C., Calmy A., Cavassini M., Dollenmaier G., Elzi L., Fehr J., Fellay J., Fux C. A., Gorgievski M., Hasse B., Hirsch H. H., Hoffmann M., Hosli I., Kahlert C., Kaiser L., Keiser O., Klimkait T., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Metzner K., Muller N., Nadal D., Nicca D., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schoni-Affolter F., Schmid P., Schupbach J., Speck R., Tarr P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S., De Luca, A, Flandre, P, Dunn, D, Zazzi, M, Wensing, A, Santoro, M, Gunthard, H, Wittkop, L, Kordossis, T, Garcia, F, Castagna, A, Cozzi-Lepri, A, Churchill, D, De Wit, S, Brockmeyer, N, Imaz, A, Mussini, C, Obel, N, Perno, C, Roca, B, Reiss, P, Schulter, E, Torti, C, van Sighem, A, Zangerle, R, Descamps, D, Mocroft, A, Kirk, O, Sabin, C, Casadi, W, Casabona, J, Miro, J, Touloumi, G, Garrido, M, Teira, R, Wit, F, Warszawski, J, Meyer, L, Dabis, F, Krause, M, Ghosn, J, Leport, C, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, del Amo, J, Thorne, C, Stephan, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, d'Arminio Monforte, A, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Haerry, D, de Wit, S, Costagliola, D, Raben, D, Chene, G, Ceccherini-Silberstein, F, Judd, A, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Davies, M, Dorrucci, M, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, van der Valk, M, Wyss, N, Aubert, V, Bernasconi, E, Boni, J, Burton-Jeangros, C, Calmy, A, Cavassini, M, Dollenmaier, G, Elzi, L, Fehr, J, Fellay, J, Fux, C, Gorgievski, M, Hasse, B, Hirsch, H, Hoffmann, M, Hosli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Metzner, K, Muller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rickenbach, M, Rudin, C, Schoni-Affolter, F, Schmid, P, Schupbach, J, Speck, R, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Weber, R, Yerly, S, University of Zurich, De Luca, Andrea, Santoro, Mm, Günthard, Hf, Brockmeyer, Nh, Perno, Cf, Schülter, E, on behalf of CHAIN and COHERE in, Eurocoord, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Infectious diseases, and Medical Microbiology and Infection Prevention
Subjects: 0301 basic medicine, Oncology, Male, Enfuvirtide, Genotyping Techniques, HIV Infections, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, 0302 clinical medicine, HIV Protease, Genotype, 2736 Pharmacology (medical), Medicine, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Non-U.S. Gov't, Darunavir, Aged, 80 and over, Microbial Sensitivity Test, Medicine (all), Research Support, Non-U.S. Gov't, Proteolytic enzymes, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Prognosis, Europe, 3004 Pharmacology, Treatment Outcome, Infectious Diseases, Mutation (genetic algorithm), Female, Human, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, Pharmacology, Prognosi, Anti-HIV Agents, 610 Medicine & health, Microbial Sensitivity Tests, Settore MED/17 - MALATTIE INFETTIVE, Research Support, Article, 03 medical and health sciences, Young Adult, Internal medicine, Linear regression, Drug Resistance, Viral, Journal Article, Humans, Aged, Receiver operating characteristic, business.industry, Anti-HIV Agent, 2725 Infectious Diseases, Raltegravir, 030112 virology, Virology, HIV Darunavir, Mutation, HIV-1, genotypic, Genotyping Technique, business
Abstract: Objectives: The objective of this studywas to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. Methods: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large European databases. HIV-1 subtype B-infected patients were used as the derivation dataset and HIV- 1 non-B-infected patients were used as the validation dataset. The adjusted association of each mutation with week 8 HIV RNA change from baseline was analysed by linear regression. A prediction model was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). Results: TCEs were selected from 681 subtype B-infected and 199 non-B-infected adults. Accompanying drugs were NRTIs in 87%, NNRTIs in 27%and raltegravir ormaraviroc or enfuvirtide in 53%. The predictionmodel included weighted protease mutations, HIV RNA, CD4 and activity of accompanying drugs. The model's association with week 8 HIV RNA change in the subtype B (derivation) set was R2=0.47 [average squared error (ASE)=0.67, P>10-6]; in the non-B (validation) set, ASE was 0.91. Accuracy investigated by means of area under the receiver operating characteristic curves with a binary response (above the threshold value of HIV RNA reduction) showed that our finalmodel outperformed models with existing interpretation systems in both training and validation sets. Conclusions: A model with a new darunavir-weighted mutation score outperformed existing GISs in both B and non-B subtypes in predicting virological response to darunavir.
Published: 2016

5. Treatment-Naive Individuals Are the Major Source of Transmitted HIV-1 Drug Resistance in Men Who Have Sex With Men in the Swiss HIV Cohort Study

Author: Drescher, Sara M., von Wyl, Viktor, Yang, Wan-Lin, Böni, Jürg, Yerly, Sabine, Shah, Cyril, Aubert, Vincent, Klimkait, Thomas, Taffé, Patrick, Furrer, Hansjakob, Battegay, Manuel, Ambrosioni, Juan, Cavassini, Matthias, Bernasconi, Enos, Vernazza, Pietro L., Ledergerber, Bruno, Günthard, Huldrych F., Kouyos, Roger D., Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C. A., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Staehelin, C., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Swiss HIV Cohort Study, Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Staehelin, C., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Kouyos, Roger D
Subjects: Microbiology (medical), Adult, Male, 10028 Institute of Medical Virology, medicine.medical_specialty, Anti-HIV Agents, Population, Sequence Homology, HIV Infections, 610 Medicine & health, Drug resistance, 2726 Microbiology (medical), Men who have sex with men, Cohort Studies, 10234 Clinic for Infectious Diseases, Young Adult, 360 Social problems & social services, Internal medicine, Genotype, Drug Resistance, Viral, medicine, Cluster Analysis, Humans, Homosexuality, Male, education, Phylogeny, ddc:616, education.field_of_study, Molecular Epidemiology, Molecular epidemiology, business.industry, Transmission (medicine), Odds ratio, 2725 Infectious Diseases, Middle Aged, 3. Good health, Infectious Diseases, pol Gene Products, Human Immunodeficiency Virus, Immunology, HIV-1, 570 Life sciences, biology, business, Switzerland, Cohort study
Abstract: BACKGROUND Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) can compromise antiretroviral therapy (ART) and thus represents an important public health concern. Typically, sources of TDR remain unknown, but they can be characterized with molecular epidemiologic approaches. We used the highly representative Swiss HIV Cohort Study (SHCS) and linked drug resistance database (SHCS-DRDB) to analyze sources of TDR. METHODS ART-naive men who have sex with men with infection date estimates between 1996 and 2009 were chosen for surveillance of TDR in HIV-1 subtype B (N = 1674), as the SHCS-DRDB contains pre-ART genotypic resistance tests for >69% of this surveillance population. A phylogeny was inferred using pol sequences from surveillance patients and all subtype B sequences from the SHCS-DRDB (6934 additional patients). Potential sources of TDR were identified based on phylogenetic clustering, shared resistance mutations, genetic distance, and estimated infection dates. RESULTS One hundred forty of 1674 (8.4%) surveillance patients carried virus with TDR; 86 of 140 (61.4%) were assigned to clusters. Potential sources of TDR were found for 50 of 86 (58.1%) of these patients. ART-naive patients constitute 56 of 66 (84.8%) potential sources and were significantly overrepresented among sources (odds ratio, 6.43 [95% confidence interval, 3.22-12.82]; P < .001). Particularly large transmission clusters were observed for the L90M mutation, and the spread of L90M continued even after the near cessation of antiretroviral use selecting for that mutation. Three clusters showed evidence of reversion of K103N or T215Y/F. CONCLUSIONS Many individuals harboring viral TDR belonged to transmission clusters with other Swiss patients, indicating substantial domestic transmission of TDR in Switzerland. Most TDR in clusters could be linked to sources, indicating good surveillance of TDR in the SHCS-DRDB. Most TDR sources were ART naive. This, and the presence of long TDR transmission chains, suggests that resistance mutations are frequently transmitted among untreated individuals, highlighting the importance of early diagnosis and treatment.
Published: 2014
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6. Protease inhibitors to treat hepatitis C in the Swiss HIV Cohort Study: high efficacy but low treatment uptake

Author: Schaerer, V, Haubitz, S, Kovari, H, Ledergerber, B, Ambrosioni, J, Cavassini, M, Stoeckle, M, Schmid, P, Decosterd, L, Aouri, M, Böni, J, Günthard, H F, Furrer, H, Metzner, K J, Fehr, J, Rauch, A, University of Zurich, and Rauch, A
Subjects: 10234 Clinic for Infectious Diseases, hepatitis C virus/HIV coinfection, treatment uptake, treatment efficacy, 10033 Clinic for Immunology, 2736 Pharmacology (medical), hepatitis C virus protease inhibitors, 610 Medicine & health, 2725 Infectious Diseases, 2719 Health Policy
Published: 2015
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7. Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case–control study using centralized ultrasensitive 454 pyrosequencing

Author: Cozzi-Lepri, Alessandro, Noguera-Julian, Marc, Di Giallonardo, Francesca, Schuurman, Rob, Däumer, Martin, Aitken, Sue, Ceccherini-Silberstein, Francesca, D'Arminio Monforte, Antonella, Geretti, Anna Maria, Booth, Clare L., Kaiser, Rolf, Michalik, Claudia, Jansen, Klaus, Masquelier, Bernard, Bellecave, Pantxika, Kouyos, Roger D., Castro, Erika, Furrer, Hansjakob, Schultze, Anna, Günthard, Huldrych F., Brun-Vezinet, Francoise, Paredes, Roger, Metzner, Karin J., Günthard, Huldrych, Brockmeyer, Norbert, Dabis, F., Bruyand, M., Chêne, G., Lawson-Ayayi, S., Thiébaut, R., Wittkop, L., André, K., Bonnal, F., Bonnet, F., Bernard, N., Caunègre, L., Cazanave, C., Ceccaldi, J., Chossat, I., Courtaud, K., Dauchy, F. A., De Witte, S., Dupon, M., Dupont, A., Duffau, P., Dutronc, H., Farbos, S., Gaborieau, V., Gemain, M. C., Gerard, Y., Greib, C., Hessamfar, M., Lacoste, D., Lataste, P., Lazaro, E., Longy-Boursier, M., Malvy, D., Meraud, J. P., Mercié, P., Monlun, E., Morlat, P., Neau, D., Ochoa, A., Pellegrin, J. L., Pistone, T., Receveur, M. C., Schmeltz, J. Roger, Tchamgoué, S., Vandenhende, M. A., Vareil, M.O., Viallard, J. F., Moreau, J. F., Pellegrin, I., Fleury, H., Lafon, M. E., Masquelier, B., Reigadas, S., Trimoulet, P., Bouchet, S., Breilh, D., Molimard, M., Titier, K., Haramburu, F., Miremont-Salamé., G., Blaizeau, M. J., Decoin, M., Delaune, J., Delveaux, S., D'Ivernois, C., Hanapier, C., Leleux, O., Lenaud, E., Uwamaliya-Nziyumvira, B., Sicard, X., Geffard, S., Le Marec, F., Conte, V., Frosch, A., Leray, J., Palmer, G., Touchard, D., Losso, M., Kundro, M., Ramos Mejia, J. M., Vetter, N., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Suetnov, O., Clumeck, N., De Wit, S., Delforge, M., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Kostov, K., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Nielsen, J., Kronborg, G., Benfield, T., Larsen, M., Gerstoft, J., Katzenstein, T., Hansen, A.-B. E., Skinhøj, P., Pedersen, C., Ostergaard, L., Dragsted, U. B., Nielsen, L. N., Zilmer, K., Smidt, Jelena, Ristola, M., Katlama, C., Viard, J. P., Girard, P. M., Vanhems, P., Pradier, C., Duvivier, C., Rockstroh, J., Schmidt, R., van Lunzen, J., Degen, O., Stellbrink, H. J., Bickel, M., Bogner, J., Fätkenheuer, G., Kosmidis, J., Gargalianos, P., Xylomenos, G., Perdios, J., Sambatakou, H., Banhegyi, D., Gottfredsson, M., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., HassounRambam, G., Elinav, H., HaouziHadassah, M., EspositoI, R., Mazzotta, F., Vullo, V., Moroni, M., Andreoni, M., Angarano, G., Antinori, A., Castelli, F., Cauda, R., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, C. F., von Schloesser, F., Viale, P., Monforte, A. D'Arminio, Castagna, A., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Ammassari, A., Balotta, C., Bonfanti, P., Bonora, S., Borderi, M., Capobianchi, M. R., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gianotti, N., Gori, A., Guaraldi, G., Lapadula, G., Lichtner, M., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Quiros Roldan, E., Rusconi, S., Cicconi, P., Fanti, I., Formenti, T., Galli, L., Lorenzini, P., Carletti, F., Carrara, S., Castrogiovanni, A., Di Caro, A., Petrone, F., Prota, G., Quartu, S., Giacometti, A., Costantini, A., Mazzoccato, S., Santoro, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Cassola, G., Viscoli, C., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Castelli, A. P., Rizzardini, G., D'Arminio Monforte, A., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Tincati, C., Puzzolante, C., Abrescia, N., Chirianni, A., Guida, M. G., Gargiulo, M., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., d'Avino, A., Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Tebano, G., Cattelan, A., Sasset, L., Mura, M. S., Rossetti, B., Caramello, P., Orofino, G. C., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Brockmeyer, N. H., Skaletz-Rorowski, A., Dupke, S., Baumgarten, A., Carganico, A., Köppe, S., Kreckel, P., Lauenroth-Mai, E., Freiwald-Rausch, M., Gölz, J., Moll, A., Zeitz, M., Hower, M., Reuter, S., Jensen, B., Harrer, T., Esser, S., Brodt, H. R., Plettenberg, A., Stöhr, A., Buhk, T., Stoll, M., Kuhlmann, B., Mosthaf, F. A., Rieke, A., Becker, W., Volkert, R., Jäger, H., Hartl, H., Mutz, A., Ulmer, A., Müller, M., Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C. A., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Staehelin, C., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Universitat de Vic. Càtedra de la Sida i Malalties Relacionades, CHAIN Minority HIV-1 Variants Working Group, Paredes, R., Metzner, KJ., Cozzi-Lepri, A., Schuurman, R., Brun-Vezinet, F., Günthard, H., Ceccherini-Silberstein, F., Kaiser, R., Geretti, AM., Brockmeyer, N., Masquelier, B., University of Zurich, and Metzner, Karin J
Subjects: Male, HIV Infections, Drug resistance, Gastroenterology, 2726 Microbiology (medical), Cohort Studies, 10234 Clinic for Infectious Diseases, chemistry.chemical_compound, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, 2736 Pharmacology (medical), Pharmacology (medical), Treatment Failure, 030212 general & internal medicine, minority drug-resistant HIV-1 variants, CHAIN, antiretroviral therapy, European multicentre study, Original Research, 0303 health sciences, High-Throughput Nucleotide Sequencing, Antiretrovirals, Sida -- Tractament, Settore MED/07 - Microbiologia e Microbiologia Clinica, Virological failure, Antiretroviral therapy, 3. Good health, Europe, Infectious Diseases, 3004 Pharmacology, Reverse Transcriptase Inhibitors, Female, Cohort study, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Efavirenz, Nevirapine, Genotype, minority drug-resistant HIV-1 variants, First line, antiretroviral therapy, 610 Medicine & health, Biology, Risk Assessment, NO, Young Adult, 03 medical and health sciences, European multicentre study, Internal medicine, Drug Resistance, Viral, Minority drug-resistant HIV-1 variants, medicine, VIH (Virus), Humans, CHAIN, 030304 developmental biology, Pharmacology, Case-control study, Computational Biology, Sequence Analysis, DNA, 2725 Infectious Diseases, Virology, chemistry, Case-Control Studies, HIV-1, Pyrosequencing
Abstract: Objectives: It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. Methods: This Europe-wide case–control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%–25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. Results: Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%),were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR¼2.75, 95% CI¼1.35–5.60, P¼0.005); similar associations were observed for at least one MV versus no NRTIMVs (OR¼2.27, 95% CI¼0.76–6.77, P¼0.140) and at least oneMV versus no NNRTIMVs (OR¼2.41, 95% CI¼1.12–5.18, P¼0.024). A dose–effect relationship between virological failure and mutational loadwas found. Conclusions: Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.
Published: 2015
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8. HIV-Infektion

Author: Tarr, P, Schmid, P, Bernasconi, E, Stoeckle, M, Kovari, H, and University of Zurich
Subjects: 10234 Clinic for Infectious Diseases, 610 Medicine & health
Published: 2015
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9. Should HIV-infected patients with unexplained chronic liver enzyme elevations be tested for hepatitis E virus? Letter reply

Author: Kovari, H, Ledergerber, B, Weber, R, University of Zurich, and Kovari, H
Subjects: 10234 Clinic for Infectious Diseases, 610 Medicine & health, 2725 Infectious Diseases, 2726 Microbiology (medical)
Published: 2010
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10. Reply to Chang and Garcia-Pagan

Author: Kovari, H, Ledergerber, B, Weber, R, University of Zurich, and Kovari, H
Subjects: 10234 Clinic for Infectious Diseases, 610 Medicine & health, 2725 Infectious Diseases, 2726 Microbiology (medical)
Published: 2010

11. Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study

Author: Kovari, H, Ledergerber, B, Peter, U, Flepp, M, Jost, J, Schmid, P, Calmy, A, Mueller, N J, Muellhaupt, B, Weber, R, University of Zurich, and Kovari, H
Subjects: 10234 Clinic for Infectious Diseases, 610 Medicine & health, 2725 Infectious Diseases, 2726 Microbiology (medical)
Abstract: Background. Noncirrhotic portal hypertension (NCPH) is a newly described life-threatening liver disease of unknown cause in human immunodeficiency virus (HIV)-infected persons. Postulated pathogenesis includes prolonged exposure to antiretroviral therapy, particularly didanosine. Methods. We performed a nested case-control study including 15 patients with NCPH and 75 matched control subjects of the Swiss HIV Cohort Study to investigate risk factors for the development of NCPH. Matching criteria were similar duration of HIV infection, absence of viral hepatitis, and follow-up to at least the date of NCPH diagnosis in the respective case. Results. All 15 case patients had endoscopically documented esophageal varices and absence of liver cirrhosis on biopsies; 4 died because of hepatic complications. At NCPH diagnosis, case patients and control subjects were similar concerning sex; race; Centers for Disease Control and Prevention stage; HIV-RNA level; CD4 cell count nadir; and lipids and lipodystrophy. Differences were found in age (conditional logistic regression odds ratio [OR] for 10 years older, 2.9; 95% confidence interval [CI], 1.4-6.1); homosexuality (OR, 4.5; 95% CI, 1.2-17); current CD4 cell count
Published: 2009
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12. The interplay between host genetic variation, viral replication and microbial translocation in untreated HIV-infected individuals

Author: Perkins, Molly R., Bartha, Istvan, Timmer, J. Katherina, Liebner, Julia C., Wollinsky, David, Günthard, Huldrych F., Hauser, Christoph, Bernasconi, Enos, Hoffmann, Matthias, Calmy, Alexandra, Battegay, Manuel, Telenti, Amalio, Douek, Daniel C., Fellay, Jacques, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, H.C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, Fellay, Jacques, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Adult, Male, Genotype, Anti-HIV Agents, CD14, Lipopolysaccharide Receptors, 610 Medicine & health, HIV Infections, Chromosomal translocation, Genome-wide association study, Biology, Fatty Acid-Binding Proteins, Virus Replication, Translocation, Genetic, 10234 Clinic for Infectious Diseases, Cohort Studies, Pathogenesis, Major Articles and Brief Reports, Immune system, Genetic variation, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/therapeutic use, Antigens, CD14/blood, Antigens, CD14/metabolism, Biological Markers/blood, Fatty Acid-Binding Proteins/blood, Fatty Acid-Binding Proteins/metabolism, Female, Gene Expression Regulation/physiology, HIV Infections/epidemiology, HIV Infections/genetics, HIV-1/physiology, Switzerland/epidemiology, Viral Load, Virus Replication/physiology, 2725 Infectious Diseases, Virology, 3. Good health, Infectious Diseases, Gene Expression Regulation, Viral replication, Immunology, 10033 Clinic for Immunology, 2723 Immunology and Allergy, HIV-1, Erratum, Viral load, Biomarkers, Switzerland
Abstract: Systemic immune activation, a major determinant of human immunodeficiency virus (HIV) disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. Although human genetic variants influencing HIV load have been identified, it is unknown how much the host genetic background contributes to interindividual differences in other determinants of HIV pathogenesis such as gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty acid–binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble CD14 (sCD14), a marker of lipopolysaccharide bioactivity and microbial translocation. We also assessed the correlations between HIV load, sCD14, and I-FABP. Although we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infection.
Published: 2015

13. Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery

Author: Aebi Popp, K, Mulcahy, F, Glass, Tr, Rudin, C, Martinez de Tejada, B, Bertisch, B, Fehr, J, Grawe, C, Scheibner, K, Rickenbach, M, Hoesli, I, Thorne, C, European Collaborative Study in EuroCoord, Swiss, Mother, Child HIV Cohort Study Collaborators: Thorne, C, Bailey, H, Giaquinto, C, Rampon, O, Mazza, A, De Rossi, A, Wörner, I, Mok, J, de José MI, Martínez, B, Peña, J, Garcia, J, Lopez, Jr, Rodriguez, Mc, Asensi Botet, F, Otero, Mc, Pérez Tamarit, D, Scherpbier, Hj, Kreyenbroek, M, Godfried, Mh, Nellen, Fj, Boer, K, Navér, L, Bohlin, Ab, Lindgren, S, Kaldma, A, Belfrage, E, Levy, J, Barlow, P, Manigart, Y, Hainaut, M, Goetghebuer, T, Brichard, B, De Camps, J, Thiry, N, Deboone, G, Waterloos, H, Viscoli, C, De Maria, A, Bentivoglio, G, Ferrero, S, Gotta, C, Mûr, A, Payà, A, López Vilchez MA, Carreras, R, Valerius, Nh, Rosenfeldt, V, Coll, O, Suy, A, Perez, J, Fortuny, C, Boguña, J, Savasi, V, Fiore, S, Crivelli, M, Viganò, A, Giacomet, V, Cerini, C, Raimondi, C, Zuccotti, G, Alberico, S, Maso, G, Tropea, M, Barresi, V, Taylor, G, Lyall, Eg, Penn, Z, Buffolano, W, Tiseo, R, Martinelli, P, Sansone, M, Maruotti, G, Agangi, A, Tibaldi, C, Marini, S, Masuelli, G, Benedetto, Chiara, Niemieç, T, Marczynska, M, Dobosz, S, Popielska, J, Oldakowska, A, Aubert, V, Barth, J, Battegay, M, Bernasconi, E, Böni, J, Brazzola, P, Bucher, Hc, Burton Jeangros, C, Calmy, A, Cavassini, M, Cheseaux, Jj, Drack, G, Duppenthaler, A, Egger, M, Elzi, L, Fellay, J, Francini, K, Furrer, H, Fux, Ca, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, Hh, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B, Metzner, K, Müller, N, Nadal, D, Pantaleo, G, Polli, Ch, Posfay Barbe, K, Rauch, A, Regenass, S, Schmid, P, Schultze, D, Schöni Affolter, F, Schüpbach, J, Speck, R, Taffé, P, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Weber, R, Wyler, Ca, Yerly, S., Posfay Barbe, Klara, Wyler, Claire-Anne, University of Zurich, Aebi-Popp, Karoline, Aebi Popp, K, Mulcahy, F, Glass, Tr, Rudin, C, Martinez de Tejada, B, Bertisch, B, Fehr, J, Grawe, C, Scheibner, K, Rickenbach, M, Hoesli, I, Buffolano, Wilma, Thorne, C, European Collaborative Study in, Eurocoord, Swiss, Mother, and Child HIV Cohort, S. t. u. d. y.
Subjects: mode of delivery, medicine.medical_treatment, HIV Infections, Delivery, Obstetric/statistics & numerical data, Virus Replication, 10234 Clinic for Infectious Diseases, Cohort Studies, HIV Infections/drug therapy/prevention & control/transmission, Pregnancy, Antiretroviral Therapy, Highly Active, 2736 Pharmacology (medical), Pharmacology (medical), Surgical Procedures, Elective/statistics & numerical data, Pregnancy Complications, Infectious, Europe, HIV, Mode of delivery, Adult, Anti-HIV Agents, Cesarean Section, Delivery, Obstetric, Drug Therapy, Combination, Elective Surgical Procedures, Female, Guidelines as Topic, Health Policy, Humans, Infant, Newborn, Infectious Disease Transmission, Vertical, Viral Load, Infectious Diseases, ddc:618, Obstetrics, Vaginal delivery, Transmission (medicine), Cesarean Section/statistics & numerical data, Meta-analysis, provvedimento amministrativo - nullità - domanda riconvenzionale, Viral load, Cohort study, medicine.medical_specialty, Pregnancy Complications, Infectious/drug therapy/epidemiology/prevention & control, 610 Medicine & health, Europe/epidemiology, Pharmacotherapy, medicine, Caesarean section, business.industry, 2725 Infectious Diseases, medicine.disease, Viral Load/drug effects, HIV, pregnancy, mode of delivery, Anti-HIV Agents/therapeutic use, Settore MED/40 - Ginecologia e Ostetricia, business, Infectious Disease Transmission, Vertical/prevention & control/statistics & numerical data
Abstract: INTRODUCTION: Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe. METHODS: In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre- or postpublication of national guidelines recommending vaginal delivery. RESULTS: Overall, 2663 women with 3013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2354) before to 7% (42/599) after the change in guidelines (P < 0.001). CONCLUSION: There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.
Published: 2013

14. Akute Harnwegsinfektionen : Teil 2 : HWI im Spital und Alters- und Pflegeheim

Author: Tarr, P, Baumann, K, Wallnöfer, A, Zimmerli, F, Maritz, D, Burri, U, Egger, M, Clerc, O, Bernasconi, E, Kovari, H, Senn, L, and University of Zurich
Subjects: 10234 Clinic for Infectious Diseases, 610 Medicine & health
Published: 2013

15. Increasing Frequency and Transmission of HIV-1 Non-B Subtypes Among Men Who Have Sex With Men in the Swiss HIV Cohort Study

Author: Duran Ramirez, Jessy J, Ballouz, Tala, Nguyen, Huyen, Kusejko, Katharina, Chaudron, Sandra E, Huber, Michael, Hirsch, Hans H, Perreau, Matthieu, Ramette, Alban, Yerly, Sabine, Cavassini, Matthias, Stöckle, Marcel, Furrer, Hansjakob, Vernazza, Pietro, Bernasconi, Enos, Günthard, Huldrych F, Kouyos, Roger D, Aebi-Popp, K, Anagnostopoulos, A, Battegay, M, Bernasconi, E, Böni, J, Braun, D L, Bucher, H C, Calmy, A, Cavassini, M, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Furrer, H, A Fux, C, Günthard, H F, Haerry, D, Hasse, B, Hirsch, H H, Hoffmann, M, Hösli, I, Huber, M, Kahlert, C R, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R D, Kovari, H, Kusejko, K, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Marzolini, C, Metzner, K J, Müller, N, Nicca, D, Paioni, P, Pantaleo, G, Perreau, M, Rauch, A, Rudin, C, Schmid, P, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Weber, R, Yerly, S, and University of Zurich
Subjects: Adult, Male, 10028 Institute of Medical Virology, medicine.medical_specialty, Maximum likelihood, Human immunodeficiency virus (HIV), HIV Infections, 610 Medicine & health, Newly diagnosed, medicine.disease_cause, Men who have sex with men, Cohort Studies, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, HIV Seropositivity, medicine, Disease Transmission, Infectious, Immunology and Allergy, Humans, 030212 general & internal medicine, MSM, Prospective Studies, Homosexuality, Male, Phylogeny, 030304 developmental biology, ddc:616, 0303 health sciences, Molecular Epidemiology, Molecular epidemiology, Transmission (medicine), business.industry, Public health, virus diseases, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 3. Good health, Non-B subtypes, Infectious Diseases, HIV-1, 570 Life sciences, biology, business, Transmission cluster, 610 Medizin und Gesundheit, Switzerland, Demography, Cohort study, 570 Biowissenschaften, Biologie
Abstract: Background In Switzerland, HIV-1 transmission among men who have sex with men (MSM) has been dominated by subtype B, whilst non-B subtypes are commonly attributed to infections acquired abroad among heterosexuals. Here, we evaluated the temporal trends of non-B subtypes and the characteristics of molecular transmission clusters (MTCs) among MSM. Methods Sociodemographic and clinical data and partial pol sequences were obtained from participants enrolled in the Swiss HIV Cohort Study. For non-B subtypes, maximum likelihood trees were constructed, from which Swiss MTCs were identified and analyzed by transmission group. Results Non-B subtypes were identified in 8.1% (416/5116) of MSM participants. CRF01_AE was the most prevalent strain (3.5%), followed by subtype A (1.2%), F (1.1%), CRF02_AG (1.1%), C (0.9%), and G (0.3%). Between 1990 and 2019, an increase in the proportion of newly diagnosed individuals (0/123 [0%] to 11/32 [34%]) with non-B subtypes in MSM was found. Across all non-B subtypes, the majority of MSM MTCs were European. Larger MTCs were observed for MSM than heterosexuals. Conclusions We found a substantial increase in HIV-1 non-B subtypes among MSM in Switzerland and the occurrence of large MTCs, highlighting the importance of molecular surveillance in guiding public health strategies targeting the HIV-1 epidemic.
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16. Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study

Author: Bertisch, B., silvia franceschi, Lise, M., Vernazza, P., Keiser, O., Schöni-Affolter, F., Bouchardy, C., Dehler, S., Levi, F., Jundt, G., Ess, S., Pawlita, M., Kovari, H., Wandeler, G., Calmy, A., Cavassini, M., Stöckle, M., Clifford, G., Hiv, Swiss Cohort Study Investigators, University of Zurich, and Bertisch, Barbara
Subjects: Male, Epidemiology, Anal Carcinoma, Original Contributions, HIV Infections, Comorbidity, Men who have sex with men, 10234 Clinic for Infectious Diseases, Switzerland/epidemiology, 0302 clinical medicine, Risk Factors, Antiretroviral Therapy, Highly Active, Antiretroviral Therapy, Highly Active/adverse effects/statistics & numerical data, 030212 general & internal medicine, Substance Abuse, Intravenous, Immunodeficiency, ddc:616, Human papillomavirus 16, Incidence, Smoking, Middle Aged, Anus Neoplasms, 3. Good health, 030220 oncology & carcinogenesis, Female, Smoking/adverse effects/epidemiology, Switzerland, Cohort study, Adult, medicine.medical_specialty, 610 Medicine & health, Immunocompromised Host, 03 medical and health sciences, 360 Social problems & social services, Internal medicine, 10049 Institute of Pathology and Molecular Pathology, medicine, Humans, Anal cancer, Homosexuality, Male, Anus Neoplasms/epidemiology/etiology/virology, Substance Abuse, Intravenous/complications, ddc:613, Gynecology, business.industry, Papillomavirus Infections, HIV Infections/complications/drug therapy/epidemiology, Papillomavirus Infections/complications/transmission/virology, Cancer, Odds ratio, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), medicine.disease, CD4 Lymphocyte Count, Homosexuality, Male/statistics & numerical data, Case-Control Studies, Nested case-control study, Human papillomavirus 16/isolation & purification/pathogenicity, business, 2713 Epidemiology
Abstract: Anal cancer is common among people infected with human immunodeficiency virus (HIV). This cancer is caused by human papillomavirus, and immunosuppression likely contributes to its development. In this issue of the Journal, Bertisch et al. (Am J Epidemiol. 2013;178(6):877–884) present the results of a case-control study of anal cancer among HIV-infected people in Switzerland. They demonstrate that anal cancer risk is increased in association with a low CD4+ cell count (a clinical measurement of immune status). In particular, HIV-induced immunosuppression was most severe among cases approximately 6–7 years prior to the diagnosis of anal cancer. A plausible biological interpretation is that immunosuppression is important at an early stage of the development of anal cancer, but that the neoplastic process becomes irreversible over time with persistent human papillomavirus infection and genetic damage. With current efforts to provide earlier combination antiretroviral therapy to HIV-infected people, anal cancer incidence may start to decline. Bertisch et al. also demonstrate a strong association between serum antibodies against the human papillomavirus type 16 protein E6 and anal cancer risk, highlighting the role of this viral oncoprotein in carcinogenesis. Additional biomarkers could help refine clinical approaches to anal cancer screening and prevention for the HIV-infected population.
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17. Developing and testing a Corona VaccinE tRiAL pLatform (COVERALL) to study Covid-19 vaccine response in immunocompromised patients

Author: Katharina, Kusejko, Frédérique, Chammartin, Daniel, Smith, Marc, Odermatt, Julian, Schuhmacher, Michael, Koller, Huldrych F, Günthard, Matthias, Briel, Heiner C, Bucher, Benjamin, Speich, Patrick, Yerly, Swiss HIV Cohort Study, Swiss Transplant Cohort Study, Abela, I., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Hachfeld, A., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Kusejko, K., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nemeth, J., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Wandeler, G., Yerly, S., Amico, P., Aubert, J.D., Banz, V., Beckmann, S., Beldi, G., Berger, C., Berishvili, E., Berzigotti, A., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Catana, E., Cairoli, A., Chalandon, Y., De Geest, S., De Rougemont, O., De Seigneux, S., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Golshayan, D., Goossens, N., Halter, FHJ, Heim, D., Hess, C., Hillinger, S., Hirt, P., Hofbauer, G., Huynh-Do, U., Immer, F., Koller, M., Laager, M., Laesser, B., Lamoth, F., Lehmann, R., Leichtle, A., Manuel, O., Marti, H.P., Martinelli, M., McLin, V., Mellac, K., Merçay, A., Mettler, K., Müller, A., Mueller, N.J., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Oldani, G., Pascual, M., Passweg, J., Pazeller, R., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schachtner, T., Schanz, U., Schaub, S., Scherrer, A., Schnyder, A., Schuurmans, M., Schwab, S., Sengstag, T., Simonetta, F., Stampf, S., Steiger, J., Stirnimann, G., Stürzinger, U., Van Delden, C., Venetz, J.P., Villard, J., Vionnet, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, and Kusejko, Katharina
Subjects: 10028 Institute of Medical Virology, COVID-19 Vaccines, SARS-CoV-2, COVID-19, 610 Medicine & health, 2725 Infectious Diseases, 10234 Clinic for Infectious Diseases, Cohort Studies, Immunocompromised Host, Treatment Outcome, 10032 Clinic for Oncology and Hematology, 10209 Clinic for Cardiology, Humans, 10178 Clinic for Pneumology, COVID-19/prevention & control, HIV, Immunocompromised, REDCap, Transplant patients, Trial platform
Abstract: BACKGROUND The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. METHODS We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. RESULTS Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. CONCLUSION Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size.
Published: 2022
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18. Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART

Author: Laura N Walti, Susana Posada Céspedes, Enos Bernasconi, Pietro Vernazza, Chenjie Wan, Matthieu Perreau, Huldrych F. Günthard, François Blanquart, Nadine Bachmann, Sabine Yerly, Teja Turk, Jacques Fellay, Volker Roth, Thomas Klimkait, Manuel Battegay, Jasmina Bogojeska, Niko Beerenwinkel, Venelin Mitov, Karin J. Metzner, Kathrin Neumann, Matthias Cavassini, Jürg Böni, Alexandra Calmy, Roger D. Kouyos, University hospital of Zurich [Zurich], Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, Kouyos, Roger D, Kaiser, Laurent, Swiss HIV Cohort Study, Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., de Tejada, B.M., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.
Subjects: 10028 Institute of Medical Virology, CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Viral/genetics, Time Factors, Statistical methods, Human immunodeficiency virus (HIV), General Physics and Astronomy, HIV Infections, medicine.disease_cause, Genome, 10234 Clinic for Infectious Diseases, Cohort Studies, Viral, lcsh:Science, ddc:616, Multidisciplinary, virus diseases, HIV-1/drug effects/genetics, Viral Load, 3100 General Physics and Astronomy, 3. Good health, Phylogenetics, Anti-Retroviral Agents, Cohort, Anti-Retroviral Agents/pharmacology, Female, Adult, Science, 030106 microbiology, 610 Medicine & health, 1600 General Chemistry, Genome, Viral, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, CD4-Positive T-Lymphocytes/virology, DNA, Viral/genetics, HIV Infections/virology, HIV-1/drug effects, HIV-1/genetics, Humans, 1300 General Biochemistry, Genetics and Molecular Biology, medicine, ddc:613, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], DNA, General Chemistry, Heritability, Term (time), 030104 developmental biology, Evolutionary biology, DNA, Viral, HIV-1, lcsh:Q
Abstract: The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients’ hurdle towards a cure., The HIV reservoir is a major hurdle for a cure of HIV, but the factors determining its size and dynamics remain unclear. Here the authors show in a large cohort of 610 HIV-1 infected individuals, who are on suppressive ART for a median of 5.4 years, that viral genetic factors contribute substantially to the HIV-1 reservoir size.
Published: 2020
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19. Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis

Author: Hovaguimian, Frédérique, Günthard, Huldrych F, Hauser, Christoph, Conen, Anna, Bernasconi, Enos, Calmy, Alexandra, Cavassini, Matthias, Seneghini, Marco, Marzel, Alex, Heinrich, Henriette, Scherrer, Alexandra, Riou, Julien, Spoerri, Adrian, Schmidlin, Kurt, Balakrishna, Suraj, Braun, Dominique L, Rampini, Silvana K, Fehr, Jan S, Kouyos, Roger D, Swiss HIV Cohort Study, University of Zurich, Hovaguimian, Frédérique, Swiss HIV Cohort Study, Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.
Subjects: 0301 basic medicine, 10028 Institute of Medical Virology, Data Analysis, Male, Pediatrics, Epidemiology, medicine.medical_treatment, Human immunodeficiency virus (HIV), General Physics and Astronomy, HIV Infections, medicine.disease_cause, Men who have sex with men, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, 610 Medicine & health, First episode, Multidisciplinary, Probabilistic data networks, virus diseases, 3100 General Physics and Astronomy, cardiovascular system, Female, Post-Exposure Prophylaxis, 360 Social problems & social services, Cohort study, circulatory and respiratory physiology, Adult, medicine.medical_specialty, Science, education, MEDLINE, 1600 General Chemistry, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, medicine, Humans, Post-exposure prophylaxis, Preventive medicine, business.industry, General Chemistry, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 030112 virology, HIV Infections/diagnosis, HIV Infections/prevention & control, Long term risk, Observational study, 10029 Clinic and Policlinic for Internal Medicine, business
Abstract: Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis., Individuals seeking post-exposure prophylaxis (PEP) for HIV may represent an important risk group for future HIV infection. Here the authors find HIV infections at long-term follow-up in 22 of 348 men who have sex with men, and 0 of 623 other PEP seekers.
Published: 2020
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20. Repeated syphilis episodes in HIV-infected men who have sex with men: a multicenter prospective cohort study on risk factors and the potential role of syphilis immunity

Author: Roth, Jan A, Franzeck, Fabian C, Balakrishna, Suraj, Lautenschlager, Stephan, Thurnheer, Maria Christine, Trellu, Laurence Toutous, Cavassini, Matthias, Vernazza, Pietro, Bernasconi, Enos, Braun, Dominique, Kouyos, Roger D, Battegay, Manuel, Swiss HIV Cohort Study, University of Zurich, Battegay, Manuel, Swiss HIV Cohort Study (SHCS), Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.
Subjects: 0301 basic medicine, 10028 Institute of Medical Virology, medicine.medical_specialty, 030106 microbiology, syphilis, 610 Medicine & health, Men who have sex with men, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Major Article, Syphilis, 030212 general & internal medicine, Risk factor, Prospective cohort study, repeated infection, ddc:616, Transmission (medicine), business.industry, Hazard ratio, Immunity, HIV, immunity, risk factor, medicine.disease, 3. Good health, Infectious Diseases, 2728 Neurology (clinical), Oncology, Repeated infection, 2730 Oncology, business, Cohort study
Abstract: BackgroundSyphilis is re-emerging globally in general and HIV-infected populations, and repeated syphilis episodes may play a central role in syphilis transmission among core groups. Besides sexual behavioral factors, little is known about determinants of repeated syphilis episodes in HIV-infected individuals—including the potential impact of preceding syphilis episodes on subsequent syphilis risk.MethodsIn the prospective Swiss HIV cohort study, with routine syphilis testing since 2004, we analyzed HIV-infected men who have sex with men (MSM). Our primary outcome was first and repeated syphilis episodes. We used univariable and multivariable Andersen-Gill models to evaluate risk factors for first and repeated incident syphilis episodes.ResultsWithin the 14-year observation period, we included 2513 HIV-infected MSM with an initially negative syphilis test. In the univariable and multivariable analysis, the number of prior syphilis episodes (adjusted hazard ratio [aHR] per 1-episode increase, 1.15; 95% confidence interval [CI], 1.01–1.31), having occasional sexual partners with or without condomless anal sex (aHR, 4.99; 95% CI, 4.08–6.11; and aHR, 2.54; 95% CI, 2.10–3.07), and being currently on antiretroviral therapy (aHR, 1.62; 95% CI, 1.21–2.16) were associated with incident syphilis.ConclusionsIn HIV-infected MSM, we observed no indication of decreased syphilis risk with repeated syphilis episodes. The extent of sexual risk behavior over time was the strongest risk factor for repeated syphilis episodes. The observed association of antiretroviral therapy with repeated syphilis episodes warrants further immunological and epidemiological investigation.
Published: 2020
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21. Rates and predictors of switching to tenofovir alafenamide-containing ART in a nationwide cohort

Author: Surial, Bernard, Cavassini, Matthias, Calmy, Alexandra, Fehr, Jan, Stöckle, Marcel, Bernasconi, Enos, Roth, Bianca, Fux, Christoph A, Kovari, Helen, Furrer, Hansjakob, Rauch, Andri, Wandeler, Gilles, Swiss HIV Cohort Study, Swiss HIV Cohort Study, Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., Yerly, S., University of Zurich, and Wandeler, Gilles
Subjects: Male, 0301 basic medicine, HIV Infections, Logistic regression, Cohort Studies, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Risk Factors, Drug Interactions, Tenofovir alafenamide, 030212 general & internal medicine, Alanine, Reverse-transcriptase inhibitor, Switch, Middle Aged, Antiretroviral therapy, 3. Good health, Infectious Diseases, Cohort, Female, Adenine/analogs & derivatives, Adenine/therapeutic use, Adult, Anti-HIV Agents/therapeutic use, CD4 Lymphocyte Count, HIV Infections/complications, HIV Infections/drug therapy, Hepatitis C, Chronic/complications, Hepatitis C, Chronic/pathology, Humans, Switzerland, Tenofovir/adverse effects, Tenofovir/therapeutic use, Tenofovir disoproxil fumarate, Toxicity, Research Article, medicine.drug, Cohort study, medicine.medical_specialty, Anti-HIV Agents, 610 Medicine & health, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 360 Social problems & social services, Internal medicine, medicine, lcsh:RC109-216, Tenofovir, business.industry, Adenine, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 2725 Infectious Diseases, Odds ratio, Hepatitis C, Chronic, 030112 virology, Confidence interval, Regimen, 10036 Medical Clinic, business
Abstract: BackgroundTenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or impaired renal function.MethodsWe included all participants of the Swiss HIV Cohort Study on TDF-containing antiretroviral therapy with follow-up visits after January 2016. We determined the proportion of switches from TDF to TAF overall, and among patients with risk factors for TDF toxicity, including osteoporosis, impaired renal function or marked proteinuria. We used multivariable logistic regression to explore predictors of switching from TDF to TAF.ResultsWe included 5′012 patients, of whom 652 (13.0%) had risk factors for TDF toxicity. A switch from TDF to TAF was undertaken in 2′796 (55.8%) individuals overall, and in 465 (71.3%) with risk factors. Predictors of switching to TAF were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.07–1.50), age > 50 years (1.43, 1.23–1.66) and the presence of risk factors for TDF toxicity (2.21, 1.77–2.75). In contrast, patients with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-pill regimen (0.11, 0.09–0.13), those treated in non-tertiary care centers (0.56, 0.46–0.70), as well as those with CD4 cell counts below 500/μL (0.77, 0.66–0.90) and with chronic hepatitis C infection (0.66, 0.54–0.80) were most likely to stay on TDF.ConclusionsOver 50% of patients on TDF-containing therapy, including the majority of patients at risk for TDF toxicity, were switched to TAF within two years of its introduction in Switzerland. Individuals on NNRTI-based single-pill regimens were most likely to remain on TDF.
Published: 2019
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22. Determinants of HIV-1 reservoir size and long-term dynamics during suppressive ART

Author: Valentina Vongrad, Nadine Bachmann, Matthieu Perreau, Sabine Yerly, Huldrych F. Günthard, Volker Roth, Mario Wieser, Thomas Klimkait, Alessandro Borghesi, Jaques Fellay, Niko Beerenwinkel, Jasmina Bogojeska, Chantal von Siebenthal, Jürg Böni, Enos Bernasconi, Sonali Parbhoo, Manuel Battegay, Andri Rauch, Roger D. Kouyos, Christian W. Thorball, Teja Turk, Yik Lim Kok, Karin J. Metzner, Kathrin Neumann, Matthias Cavassini, Matthias Hoffmann, University of Zurich, Günthard, Huldrych F, Swiss HIV Cohort Study, Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Tejada, B.M., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.
Subjects: 0301 basic medicine, 10028 Institute of Medical Virology, Male, Population level, Human immunodeficiency virus (HIV), General Physics and Astronomy, HIV Infections, 02 engineering and technology, Pathogenesis, medicine.disease_cause, 10234 Clinic for Infectious Diseases, Longitudinal Studies, lcsh:Science, 610 Medicine & health, ddc:616, Multidisciplinary, Middle Aged, Viral Load, 021001 nanoscience & nanotechnology, 3100 General Physics and Astronomy, Virus Latency, RNA, Viral, Female, 0210 nano-technology, Viral load, Adult, Anti-HIV Agents, Science, Alpha interferon, Viremia, 1600 General Chemistry, Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, Plasma viral load, 03 medical and health sciences, Medical research, 1300 General Biochemistry, Genetics and Molecular Biology, medicine, Humans, Disease Reservoirs, General Chemistry, medicine.disease, Antiretroviral therapy, 030104 developmental biology, 10036 Medical Clinic, Immunology, HIV-1, lcsh:Q
Abstract: The HIV-1 reservoir is the major hurdle to a cure. We here evaluate viral and host characteristics associated with reservoir size and long-term dynamics in 1,057 individuals on suppressive antiretroviral therapy for a median of 5.4 years. At the population level, the reservoir decreases with diminishing differences over time, but increases in 26.6% of individuals. Viral blips and low-level viremia are significantly associated with slower reservoir decay. Initiation of ART within the first year of infection, pretreatment viral load, and ethnicity affect reservoir size, but less so long-term dynamics. Viral blips and low-level viremia are thus relevant for reservoir and cure studies., Nature Communications, 10 (1), ISSN:2041-1723
Published: 2019
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23. Mortality from suicide among people living with HIV and the general Swiss population: 1988-2017

Author: Ruffieux, Yann, Lemsalu, Liis, Aebi-Popp, Karoline, Calmy, Alexandra, Cavassini, Matthias, Fux, Christoph A, Günthard, Huldrych F, Marzolini, Catia, Scherrer, Alexandra, Vernazza, Pietro, Keiser, Olivia, Egger, Matthias, Swiss HIV Cohort Study, Swiss National Cohort Study Group, Swiss HIV Cohort Study and the Swiss National Cohort, Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Ciuffi, A., Dollenmaier, G., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Wandeler, G., Weber, R., Yerly, S.T., University of Zurich, and Egger, Matthias
Subjects: Adult, Male, 10028 Institute of Medical Virology, Short Report, Intravenous drug use, HIV Infections, 610 Medicine & health, Cohort Studies, 10234 Clinic for Infectious Diseases, Short Reports, Risk Factors, 360 Social problems & social services, Antiretroviral Therapy, Highly Active, Humans, intravenous drug use, comparative study, ddc:613, ddc:616, virus diseases, HIV, 2739 Public Health, Environmental and Occupational Health, 2725 Infectious Diseases, Middle Aged, Anti-Retroviral Agents/therapeutic use, Antiretroviral Therapy, Highly Active/methods, Female, HIV Infections/drug therapy, HIV Infections/mortality, Suicide/statistics & numerical data, Switzerland/epidemiology, SMR, Switzerland, suicide, Suicide, Anti-Retroviral Agents, 10036 Medical Clinic, Comparative study
Abstract: Introduction In many countries, mortality due to suicide is higher among people living with HIV than in the general population. We aimed to analyse trends in suicide mortality before and after the introduction of triple combination antiretroviral therapy (cART), and to identify risk factors associated with death from suicide in Switzerland. Methods We analysed data from the Swiss HIV Cohort Study from the pre‐cART (1988‐1995), earlier cART (1996‐2008) and later cART (2009‐2017) eras. We used multivariable Cox regression to assess risk factors for death due to suicide in the ART era and computed standardized mortality ratios (SMRs) to compare mortality rates due to suicide among persons living with HIV with the general population living in Switzerland, using data from the Swiss National Cohort. Results and Discussion We included 20,136 persons living with HIV, of whom 204 (1.0%) died by suicide. In men, SMRs for suicide declined from 12.9 (95% CI 10.4‐16.0) in the pre‐cART era to 2.4 (95% CI 1.2‐5.1) in the earlier cART and 3.1 (95% CI 2.3‐4.3) in the later cART era. In women, the corresponding ratios declined from 14.2 (95% CI 7.9‐25.7) to 10.2 (3.8‐27.1) and to 3.3 (95% CI 1.5‐7.4). Factors associated with death due to suicide included gender (adjusted hazard ratio 0.58 (95% CI 0.38‐0.87) comparing women with men), nationality (1.95 (95% CI 1.34‐2.83) comparing Swiss with other), Centers for Disease Control and Prevention clinical stage (0.33 (95% CI 0.24‐0.46) comparing stage A with C), transmission group (2.64 (95% CI 1.71‐4.09) for injection drug use and 2.10 (95% CI 1.36‐3.24) for sex between men compared to other), and mental health (2.32 (95% CI 1.71‐3.14) for a history of psychiatric treatment vs. no history). There was no association with age. Conclusions Suicide rates have decreased substantially among people living with HIV in the last three decades but have remained about three times higher than in the general population since the introduction of cART. Continued emphasis on suicide prevention among men and women living with HIV is important.
Published: 2019
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24. Impact of Direct-Acting Antivirals on the Burden of HCV Infection Among Persons Who Inject Drugs and Men Who Have Sex With Men in the Swiss HIV Cohort Study

Author: Marcel Stoeckle, Gilles Wandeler, Luisa Salazar-Vizcaya, Jan Fehr, Matthias Hoffmann, Enos Bernasconi, Mathieu Rougemont, Matthias Cavassini, Andri Rauch, Charles Béguelin, Dominique L Braun, University of Zurich, Béguelin, Charles, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Pantaleo, G., Paioni, P., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.
Subjects: medicine.medical_specialty, Hepatitis C virus, Human immunodeficiency virus (HIV), 610 Medicine & health, medicine.disease_cause, DIRECT ACTING ANTIVIRALS, Men who have sex with men, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, 360 Social problems & social services, Internal medicine, medicine, MSM, 030212 general & internal medicine, PWID, DAA, business.industry, Brief Report, virus diseases, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Hepatitis C, medicine.disease, 3. Good health, 2728 Neurology (clinical), Infectious Diseases, Oncology, Viral replication, HCV, viral replication, 2730 Oncology, 030211 gastroenterology & hepatology, business, Cohort study
Abstract: In the Swiss HIV Cohort Study, the number of people who inject drugs with replicating hepatitis C virus (HCV) infection decreased substantially after the introduction of direct-acting antivirals (DAAs). Among men who have sex with men, the increase in DAA uptake and efficacy was counterbalanced by frequent incident HCV infections.
Published: 2018
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25. The cumulative impact of harm reduction on the swiss HIV epidemic: cohort study, mathematical model, and phylogenetic analysis

Author: Marzel, Alex, Kusejko, Katharina, Weber, Rainer, Bruggmann, Philip, Rauch, Andri, Roth, Jan A, Bernasconi, Enos, Calmy, Alexandra, Cavassini, Matthias, Hoffmann, Matthias, Böni, Jürg, Yerly Ferrillo, Sabine, Klimkait, Thomas, Perreau, Matthieu, Günthard, Huldrych F, Kouyos, Roger D, Swiss HIV Cohort Study, Swiss HIV Cohort Study, Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., Yerly, S., University of Zurich, and Kouyos, Roger D
Subjects: 0301 basic medicine, 10028 Institute of Medical Virology, 030106 microbiology, Population, HIV, harm reduction, injecting drug use, needle and syringe exchange, opioids, 610 Medicine & health, Disease cluster, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Major Article, Medicine, 030212 general & internal medicine, education, ddc:616, education.field_of_study, Harm reduction, business.industry, Transmission (medicine), Needle and syringe exchange, Incidence (epidemiology), Outbreak, virus diseases, medicine.disease, 3. Good health, Opioids, Editor's Choice, Infectious Diseases, 2728 Neurology (clinical), Oncology, 10036 Medical Clinic, Injecting drug use, 2730 Oncology, business, Demography, Cohort study
Abstract: BackgroundHuman immunodeficiency virus (HIV) transmission among injecting drug users (IDUs) is increasing in the United States due to the recent opioid epidemic and is the leading mode of transmission in Eastern Europe.MethodsTo evaluate the overall impact of HIV harm reduction, we combined (1) data from the Swiss HIV Cohort Study and public sources with (2) a mathematical model expressed as a system of ordinary differential equations. The model reconstructs the national epidemic from the first case in 1980 until 2015. Phylogenetic cluster analysis of HIV-1 pol sequences was used to quantify the epidemic spillover from IDUs to the general population.ResultsOverall, harm reduction prevented 15903 (range, 15359–16448) HIV infections among IDUs until the end of 2015, 5446 acquired immune deficiency syndrome (AIDS) deaths (range, 5142–5752), and a peak HIV prevalence of 50.7%. Introduction of harm reduction 2 years earlier could have halved the epidemic, preventing 3161 (range, 822–5499) HIV infections and 1468 (range, 609–2326) AIDS deaths. Suddenly discontinuing all harm reduction in 2005 would have resulted in outbreak re-emergence with 1351 (range, 779–1925) additional HIV cases. Without harm reduction, the estimated additional number of heterosexuals infected by HIV-positive IDUs is estimated to have been 2540 (range, 2453–2627), which is equivalent to the total national reported incidence among heterosexuals in the period of 2007 to 2015.ConclusionsOur results suggest that a paramount, population-level impact occurred because of the harm reduction package, beyond factors that can be explained by a reduction in risk behavior and a decrease in the number of drug users over time.
Published: 2018
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26. Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study

Author: Yang Wan-Lin, Kouyos Roger D., Scherrer Alexandra U., Boeni Juerg, Shah Cyril, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Hirzel Cedric, Battegay Manuel, Cavassini Matthias, Bernasconi Enos, Vernazza Pietro, Held Leonhard, Ledergerber Bruno, Guenthard Huldrych F., Study Swiss HIV Cohort, University of Zurich, Swiss HIV Cohort Study (SHCS), Swiss HIV Cohort Study SHCS, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Male, 10028 Institute of Medical Virology, Adult, Antiretroviral Therapy, Highly Active/methods, Drug Resistance, Viral, Female, HIV Infections/drug therapy, HIV-1, Humans, Middle Aged, Nucleosides/therapeutic use, Nucleotides/therapeutic use, Reverse Transcriptase Inhibitors/therapeutic use, Switzerland, Treatment Failure, Drug Resistance, HIV Infections, 01 natural sciences, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, Abacavir, Antiretroviral Therapy, Highly Active, 2736 Pharmacology (medical), Medicine, Pharmacology (medical), Viral, 030212 general & internal medicine, ddc:616, education.field_of_study, Nucleotides, virus diseases, Lamivudine, Nucleosides, 3. Good health, 3004 Pharmacology, Infectious Diseases, Reverse Transcriptase Inhibitors, medicine.drug, Microbiology (medical), medicine.medical_specialty, Highly Active/methods, Efavirenz, Nevirapine, Population, Antiretroviral Therapy, 610 Medicine & health, Emtricitabine, 03 medical and health sciences, Zidovudine, Internal medicine, 0101 mathematics, education, Pharmacology, business.industry, 010102 general mathematics, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 2725 Infectious Diseases, Lamivudine/Zidovudine, Virology, chemistry, 10033 Clinic for Immunology, business
Abstract: BACKGROUND The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare. METHODS We included patients starting first-line combination ART (cART) with or switching from first-line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency. RESULTS Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02). CONCLUSIONS Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden.
Published: 2015
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27. Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The Swiss HIV Cohort Study

Author: Cornelia, Bayard, Bruno, Ledergerber, Markus, Flepp, Thanh, Lecompte, Estelle, Moulin, Matthias, Hoffmann, Rainer, Weber, Cornelia, Staehelin, Caroline, Di Benedetto, Christoph A, Fux, Philip E, Tarr, Barbara, Hasse, S, Yerly, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Pantaleo, G., Paioni, P., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., Yerly, S., University of Zurich, and Hasse, Barbara
Subjects: 0301 basic medicine, medicine.medical_specialty, 030106 microbiology, Population, antiretroviral therapy, 610 Medicine & health, avascular bone necrosis, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Major Article, Medicine, 030212 general & internal medicine, Risk factor, education, ddc:616, education.field_of_study, business.industry, Incidence (epidemiology), Case-control study, HIV, Odds ratio, Confidence interval, tenofovir, 3. Good health, Surgery, 2728 Neurology (clinical), Infectious Diseases, Oncology, 2730 Oncology, business, Viral load, Cohort study
Abstract: BackgroundHIV-infected individuals have an increased risk of avascular bone necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors (PI) have been implicated as a risk factor. We aimed to study the associations of ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS).MethodsWe used incidence density sampling to perform a case control study within the Swiss HIV Cohort Study (SHCS) comparing prospectively collected AVN cases and controls by conditional logistic regression analysis. To evaluate the effect of ART, multivariable models were adjusted for HIV transmission risk group, age, alcohol consumption, use of corticosteroids, CD4 nadir, maximum viral load, and pancreatitis.ResultsWe compared 74 AVN cases and 145 controls. Associations with AVN were shown for heterosexual HIV acquisition (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1–10), alcohol consumption (OR, 2.7; 95% CI, 1.3–5.7), and hyperlipidemia (OR, 3.6; 95% CI, 1.4–9.6). After adding ART substances to the multivariable base model, there was evidence of an association for treatment with tenofovir (TDF) >1 year (OR, 4.4; 95% CI, 1.4–14) with AVN. Neither exposure to specific frequently prescribed ART combinations or ART drug classes nor cumulative ART exposure showed any associations with AVN.ConclusionsIn the HIV-infected population, a combination of risk factors such as heterosexual HIV acquisition, moderate to severe alcohol intake, and hyperlipidemia seem to contribute to AVN. ART does not seem to be a relevant risk factor for AVN. The association of prolonged TDF exposure with AVN needs to be confirmed.
Published: 2017
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28. Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV

Author: Kouyos, Roger D, Rauch, Andri, Böni, Jürg, Yerly, Sabine, Shah, Cyril, Aubert, Vincent, Klimkait, Thomas, Kovari, Helen, Calmy, Alexandra, Cavassini, Matthias, Battegay, Manuel, Vernazza, Pietro L, Bernasconi, Enos, Ledergerber, Bruno, Günthard, Huldrych F, Egger, Matthias, Furrer, Hansjakob, Keiser, Olivia, Schöni-Affolter, Franziska, Swiss HIV Cohort Study, Swiss HIV Cohort Study (SHCS), Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Burton-Jeangros, Claudine, Hirschel, Bernard, Kaiser, Laurent, Martinez De Tejada Weber, Begona, University of Zurich, and Kouyos, Roger D
Subjects: 10028 Institute of Medical Virology, Male, Epidemiology, HIV Infections, Hepacivirus, Men who have sex with men, 10234 Clinic for Infectious Diseases, Cohort Studies, HIV-HCV coinfection, molecular epidemiology, genotypic resistance testing, sexual transmission of HCV, Substance Abuse, Intravenous, 610 Medicine & health, ddc:616, Molecular Epidemiology, Transmission (medicine), Coinfection, Reverse Transcriptase Polymerase Chain Reaction, Incidence (epidemiology), virus diseases, General Medicine, Hepatitis C, 3. Good health, RNA, Viral, Female, sexual transmission of HCV, Switzerland, 360 Social problems & social services, Cohort study, medicine.medical_specialty, Sexual transmission, Internal medicine, medicine, Humans, genotypic resistance testing, Homosexuality, Male, HCV coinfection, Codon, business.industry, HIV, Odds ratio, medicine.disease, Virology, digestive system diseases, HIV-1, 570 Life sciences, biology, business, 2713 Epidemiology
Abstract: BACKGROUND: HCV coinfection remains a major cause of morbidity and mortality among HIV-infected individuals and its incidence has increased dramatically in HIV-infected men who have sex with men(MSM). METHODS: Hepatitis C virus (HCV) coinfection in the Swiss HIV Cohort Study(SHCS) was studied by combining clinical data with HIV-1 pol-sequences from the SHCS Drug Resistance Database(DRDB). We inferred maximum-likelihood phylogenetic trees, determined Swiss HIV-transmission pairs as monophyletic patient pairs, and then considered the distribution of HCV on those pairs. RESULTS: Among the 9748 patients in the SHCS-DRDB with known HCV status, 2768(28%) were HCV-positive. Focusing on subtype B(7644 patients), we identified 1555 potential HIV-1 transmission pairs. There, we found that, even after controlling for transmission group, calendar year, age and sex, the odds for an HCV coinfection were increased by an odds ratio (OR) of 3.2 [95% confidence interval (CI) 2.2, 4.7) if a patient clustered with another HCV-positive case. This strong association persisted if transmission groups of intravenous drug users (IDUs), MSMs and heterosexuals (HETs) were considered separately(in all cases OR >2). Finally we found that HCV incidence was increased by a hazard ratio of 2.1 (1.1, 3.8) for individuals paired with an HCV-positive partner. CONCLUSIONS: Patients whose HIV virus is closely related to the HIV virus of HIV/HCV-coinfected patients have a higher risk for carrying or acquiring HCV themselves. This indicates the occurrence of domestic and sexual HCV transmission and allows the identification of patients with a high HCV-infection risk.
Published: 2014
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29. Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland

Author: Shilaih Mohaned, Marzel Alex, Yang Wan Lin, Scherrer Alexandra U., Schupbach Jorg, Boni Jurg, Yerly Sabine, Hirsch Hans H., Aubert Vincent, Cavassini Matthias, Klimkait Thomas, Vernazza Pietro L., Bernasconi Enos, Furrer Hansjakob, Gunthard Huldrych F., Kouyos Roger, Study Swiss HIV Cohort, Swiss HIV Cohort Study, Battegay, M., Braun, D., Bucher, H., Burton-Jeangros, C., Calmy, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Fux, C., Gorgievski, M., Haerry, D., Hasse, B., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Ledergerber, B., Martinetti, G., de Tejada, B.M., Marzolini, C., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rudin, C., Schöni-Affolter, F., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Weber, R., University of Zurich, and Shilaih, Mohaned
Subjects: Adult, Male, 10028 Institute of Medical Virology, 0301 basic medicine, Multivariate analysis, Genotype, Anti-HIV Agents, Anti-HIV Agents/therapeutic use, Cohort Studies, Drug Resistance, Viral/genetics, Female, HIV Infections/drug therapy, HIV Infections/epidemiology, HIV Infections/transmission, HIV Infections/virology, HIV-1/classification, HIV-1/genetics, HIV-1/isolation & purification, Heterosexuality, Homosexuality, Male, Humans, Middle Aged, Molecular Typing, Multivariate Analysis, Phylogeny, Substance Abuse, Intravenous/drug therapy, Substance Abuse, Intravenous/epidemiology, Substance Abuse, Intravenous/virology, Switzerland/epidemiology, HIV Infections, 610 Medicine & health, Biology, Logistic regression, Article, law.invention, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, law, Drug Resistance, Viral, 030212 general & internal medicine, Substance Abuse, Intravenous, ddc:616, Genetics, 1000 Multidisciplinary, Multidisciplinary, Phylogenetic tree, Outbreak, Confidence interval, 3. Good health, 030104 developmental biology, Transmission (mechanics), HIV-1, Switzerland, Demography, Cohort study
Abstract: Targeting hard-to-reach/marginalized populations is essential for preventing HIV-transmission. A unique opportunity to identify such populations in Switzerland is provided by a database of all genotypic-resistance-tests from Switzerland, including both sequences from the Swiss HIV Cohort Study (SHCS) and non-cohort sequences. A phylogenetic tree was built using 11,127 SHCS and 2,875 Swiss non-SHCS sequences. Demographics were imputed for non-SHCS patients using a phylogenetic proximity approach. Factors associated with non-cohort outbreaks were determined using logistic regression. Non-B subtype (univariable odds-ratio (OR): 1.9; 95% confidence interval (CI): 1.8–2.1), female gender (OR: 1.6; 95% CI: 1.4–1.7), black ethnicity (OR: 1.9; 95% CI: 1.7–2.1) and heterosexual transmission group (OR:1.8; 95% CI: 1.6–2.0), were all associated with underrepresentation in the SHCS. We found 344 purely non-SHCS transmission clusters, however, these outbreaks were small (median 2, maximum 7 patients) with a strong overlap with the SHCS’. 65% of non-SHCS sequences were part of clusters composed of >= 50% SHCS sequences. Our data suggests that marginalized-populations are underrepresented in the SHCS. However, the limited size of outbreaks among non-SHCS patients in-care implies that no major HIV outbreak in Switzerland was missed by the SHCS surveillance. This study demonstrates the potential of sequence data to assess and extend the scope of infectious-disease surveillance.
Published: 2016
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30. The J-Curve in HIV: Low and Moderate Alcohol Intake Predicts Mortality but Not the Occurrence of Major Cardiovascular Events

Author: Gilles, Wandeler, David, Kraus, Jan, Fehr, Anna, Conen, Alexandra, Calmy, Christina, Orasch, Manuel, Battegay, Patrick, Schmid, Enos, Bernasconi, Hansjakob, Furrer, S, Yerly, University of Zurich, Wandeler, Gilles, Swiss HIV Cohort Study, Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Alcohol Drinking, alcohol consumption, Alcohol, 610 Medicine & health, HIV Infections, Disease, 10234 Clinic for Infectious Diseases, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, 360 Social problems & social services, Internal medicine, medicine, cohort study, 2736 Pharmacology (medical), Humans, Pharmacology (medical), 030212 general & internal medicine, Dose-Response Relationship, Drug, Proportional hazards model, business.industry, Incidence (epidemiology), Alcoholic Beverages, Hazard ratio, 2725 Infectious Diseases, Middle Aged, Clinical Science, HIV infection, 030112 virology, mortality, Confidence interval, 3. Good health, Surgery, cardiovascular diseases, Infectious Diseases, chemistry, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, J curve, Cardiovascular Diseases/epidemiology, HIV Infections/complications, HIV Infections/epidemiology, Switzerland/epidemiology, business, Switzerland, Cohort study
Abstract: Supplemental Digital Content is Available in the Text., Objectives: In HIV-negative populations, light-to-moderate alcohol consumption is associated with a lower cardiovascular morbidity and mortality than alcohol abstention. Whether the same holds true for HIV-infected individuals has not been evaluated in detail. Design: Cohort study. Methods: Adults on antiretroviral therapy in the Swiss HIV Cohort Study with follow-up after August 2005 were included. We categorized alcohol consumption into: abstention or very low (
Published: 2015
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31. HBV genotypes and response to tenofovir disoproxil fumarate in HIV/HBV-coinfected persons

Author: Florian, Bihl, Gladys, Martinetti, Gilles, Wandeler, Rainer, Weber, Bruno, Ledergeber, Alexandra, Calmy, Manuel, Battegay, Matthias, Cavassini, Pietro, Vernazza, Anna-Paola, Caminada, Martin, Rickenbach, Enos, Bernasconi, S, Yerly, University of Zurich, Bihl, Florian, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Male, HIV Infections, medicine.disease_cause, 10234 Clinic for Infectious Diseases, Genotype, Young adult, 610 Medicine & health, Coinfection, Gastroenterology, Lamivudine, virus diseases, General Medicine, Hepatitis B, Middle Aged, Viral Load, Female, Adult, Aged, Antiviral Agents/therapeutic use, Coinfection/drug therapy, Coinfection/virology, Drug Resistance, Viral/genetics, HIV Infections/complications, HIV Infections/drug therapy, Hepatitis B/complications, Hepatitis B/drug therapy, Hepatitis B virus/genetics, Humans, Lamivudine/therapeutic use, Retrospective Studies, Switzerland, Tenofovir/therapeutic use, Viral Load/drug effects, Young Adult, Viral load, 360 Social problems & social services, medicine.drug, Research Article, medicine.medical_specialty, Hepatitis B virus, Antiviral Agents, Internal medicine, Drug Resistance, Viral, medicine, 2715 Gastroenterology, Tenofovir, business.industry, Hepatology, medicine.disease, Virology, digestive system diseases, Immunology, 10033 Clinic for Immunology, business
Abstract: BACKGROUND: Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood. METHODS: HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA
Published: 2015
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32. Frequency of and Risk Factors for Depression among Participants in the Swiss HIV Cohort Study (SHCS)

Author: Alexia Anagnostopoulos, Bruno Ledergerber, René Jaccard, Susy Ann Shaw, Marcel Stoeckle, Enos Bernasconi, Jürgen Barth, Alexandra Calmy, Alexandre Berney, Josef Jenewein, Rainer Weber, Swiss HIV Cohort Study, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., and University of Zurich
Subjects: Male, medicine.medical_specialty, Poison control, lcsh:Medicine, HIV Infections, 610 Medicine & health, 1100 General Agricultural and Biological Sciences, Men who have sex with men, Depression/epidemiology, Female, HIV Infections/psychology, Humans, Incidence, Logistic Models, Prospective Studies, Regression Analysis, Risk Factors, Sweden/epidemiology, 10234 Clinic for Infectious Diseases, 1300 General Biochemistry, Genetics and Molecular Biology, History of depression, Medicine, Psychiatry, Prospective cohort study, lcsh:Science, Depression (differential diagnoses), Sweden, 1000 Multidisciplinary, Multidisciplinary, Depression, business.industry, Incidence (epidemiology), lcsh:R, 3. Good health, 10034 Institute of Complementary Medicine, 10057 Klinik für Konsiliarpsychiatrie und Psychosomatik, Cohort, 10033 Clinic for Immunology, lcsh:Q, business, Research Article, Demography, Cohort study
Abstract: OBJECTIVES: We studied the incidence and prevalence of, and co-factors for depression in the Swiss HIV Cohort Study. METHODS: Depression-specific items were introduced in 2010 and prospectively collected at semiannual cohort visits. Clinical, laboratory and behavioral co-factors of incident depression among participants free of depression at the first two visits in 2010 or thereafter were analyzed with Poisson regression. Cumulative prevalence of depression at the last visit was analyzed with logistic regression. RESULTS: Among 4,422 participants without a history of psychiatric disorders or depression at baseline, 360 developed depression during 9,348 person-years (PY) of follow-up, resulting in an incidence rate of 3.9 per 100 PY (95% confidence interval (CI) 3.5-4.3). Cumulative prevalence of depression during follow-up was recorded for 1,937/6,756 (28.7%) participants. Incidence and cumulative prevalence were higher in injection drug users (IDU) and women. Older age, preserved work ability and higher physical activity were associated with less depression episodes. Mortality (0.96 per 100 PY, 95% CI 0.83-1.11) based upon 193 deaths over 20,102 PY was higher among male IDU (2.34, 1.78-3.09), female IDU (2.33, 1.59-3.39) and white heterosexual men (1.32, 0.94-1.84) compared to white heterosexual women and homosexual men (0.53, 0.29-0.95; and 0.71, 0.55-0.92). Compared to participants free of depression, mortality was slightly elevated among participants with a history of depression (1.17, 0.94-1.45 vs. 0.86, 0.71-1.03, P = 0.033). Suicides (n = 18) did not differ between HIV transmission groups (P = 0.50), but were more frequent among participants with a prior diagnosis of depression (0.18 per 100 PY, 95%CI 0.10-0.31; vs. 0.04, 0.02-0.10; P = 0.003). CONCLUSIONS: Depression is a frequent co-morbidity among HIV-infected persons, and thus an important focus of care. Language: en
Published: 2015

33. Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012

Author: Hans H. Hirsch, A. Calmy, Irene Hösli, Nicolas Müller, Manuel Battegay, Pietro Vernazza, Laurent Kaiser, G. Dollenmaier, Andri Rauch, Cyril Shah, Franziska Schöni-Affolter, Sabine Yerly, S Yerly, Olivia Keiser, Karin J. Metzner, Jörg Schüpbach, Patrick Schmid, Barbara Hasse, E Bernasconi, Roger D. Kouyos, Christian R Kahlert, Günthard Hf, Jan Fehr, Meri Gorgievski, P. Vernazza, Matthias Hoffmann, Stephan Regenass, M. Cavassini, B Martinez de Tejada, Gladys Martinetti, Jürg Böni, Hansjakob Furrer, RD Kouyos, C. A. Fux, B. Ledergerber, Leonhard Held, Christoph Rudin, Dunja Nicca, Martin Rickenbach, M Egger, Rainer Weber, Alexandra U. Scherrer, Huldrych F. Günthard, H Furrer, G. Pantaleo, Jacques Fellay, A. Telenti, D Haerry, Roberto F. Speck, Heiner C. Bucher, David Nadal, Matthias Cavassini, Vincent Aubert, Helen Kovari, Thomas Klimkait, Bruno Ledergerber, Enos Bernasconi, T Klimkait, V Aubert, L. Elzi, Philip E. Tarr, M Battegay, Alexandra Trkola, Wan-Lin Yang, Claudine Burton-Jeangros, J Böni, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Günthard, Huldrych F
Subjects: 10028 Institute of Medical Virology, Male, HIV Infections, Drug resistance, Rate ratio, 10234 Clinic for Infectious Diseases, Cohort Studies, Editorial Commentaries, 0302 clinical medicine, Prevalence, Immunology and Allergy, 030212 general & internal medicine, Prospective Studies, ddc:616, 0303 health sciences, education.field_of_study, Resistance mutation, 3. Good health, Infectious Diseases, HIV, transmission, drug resistance, recently infected, fitness, symbols, 2723 Immunology and Allergy, Female, Viral load, Cohort study, Adult, medicine.medical_specialty, Genotype, Anti-HIV Agents, Population, Mutation, Missense, 610 Medicine & health, 03 medical and health sciences, symbols.namesake, Internal medicine, Drug Resistance, Viral, medicine, Humans, Poisson regression, education, antiretroviral drugs, 030306 microbiology, business.industry, acquired resistance, Odds ratio, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 2725 Infectious Diseases, biochemical phenomena, metabolism, and nutrition, transmitted resistance, Immunology, 10033 Clinic for Immunology, HIV-1, business
Abstract: BACKGROUND: Transmitted human immunodeficiency virus type 1 (HIV) drug resistance (TDR) mutations are transmitted from nonresponding patients (defined as patients with no initial response to treatment and those with an initial response for whom treatment later failed) or from patients who are naive to treatment. Although the prevalence of drug resistance in patients who are not responding to treatment has declined in developed countries, the prevalence of TDR mutations has not. Mechanisms causing this paradox are poorly explored. METHODS: We included recently infected, treatment-naive patients with genotypic resistance tests performed ≤1 year after infection and before 2013. Potential risk factors for TDR mutations were analyzed using logistic regression. The association between the prevalence of TDR mutations and population viral load (PVL) among treated patients during 1997-2011 was estimated with Poisson regression for all TDR mutations and individually for the most frequent resistance mutations against each drug class (ie, M184V/L90M/K103N). RESULTS: We included 2421 recently infected, treatment-naive patients and 5399 patients with no response to treatment. The prevalence of TDR mutations fluctuated considerably over time. Two opposing developments could explain these fluctuations: generally continuous increases in the prevalence of TDR mutations (odds ratio, 1.13; P = .010), punctuated by sharp decreases in the prevalence when new drug classes were introduced. Overall, the prevalence of TDR mutations increased with decreasing PVL (rate ratio [RR], 0.91 per 1000 decrease in PVL; P = .033). Additionally, we observed that the transmitted high-fitness-cost mutation M184V was positively associated with the PVL of nonresponding patients carrying M184V (RR, 1.50 per 100 increase in PVL; P < .001). Such association was absent for K103N (RR, 1.00 per 100 increase in PVL; P = .99) and negative for L90M (RR, 0.75 per 100 increase in PVL; P = .022). CONCLUSIONS: Transmission of antiretroviral drug resistance is temporarily reduced by the introduction of new drug classes and driven by nonresponding and treatment-naive patients. These findings suggest a continuous need for new drugs, early detection/treatment of HIV-1 infection.
Published: 2014

34. Disentangling human tolerance and resistance against HIV

Author: Regoes, Roland R, McLaren, Paul J, Battegay, Manuel, Bernasconi, Enos, Calmy, Alexandra, Günthard, Huldrych F, Hoffmann, Matthias, Rauch, Andri, Telenti, Amalio, Fellay, Jacques, University of Zurich, Regoes, Roland R, Swiss HIV Cohort Study, Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., Staehelin, C., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Male, HIV Infections/genetics/immunology/pathology/virology, T-Lymphocytes, Population Modeling, HIV Infections, Major Histocompatibility Complex, Cohort Studies, 10234 Clinic for Infectious Diseases, Gene Frequency, HIV-1/immunology, 2400 General Immunology and Microbiology, ddc:616, Ecology, HLA-B Antigens/genetics/immunology, Homozygote, Age Factors, virus diseases, 2800 General Neuroscience, Middle Aged, Viral Load, T-Lymphocytes/immunology/pathology/virology, AIDS, Receptors, CCR5/genetics/immunology, Host-Pathogen Interactions, Disease Progression, Infectious diseases, Female, Research Article, Immune Tolerance/genetics, Adult, Heterozygote, Evolutionary Immunology, Receptors, CCR5, Immunology, 610 Medicine & health, Viral diseases, 1100 General Agricultural and Biological Sciences, Sex Factors, 1300 General Biochemistry, Genetics and Molecular Biology, Immune Tolerance, Humans, Alleles, Medicine and health sciences, Evolutionary Biology, Polymorphism, Genetic, Population Biology, Genome, Human, Biology and Life Sciences, Computational Biology, Immunity, Innate, CD4 Lymphocyte Count, Evolutionary Ecology, HLA-B Antigens, HIV-1, Clinical Immunology, Immunity, Innate/genetics, Infectious Disease Modeling
Abstract: Title: Human tolerance against HIV An evolutionary ecology perspective on clinical data reveals that human traits can affect how well an individual tolerates HIV infection, and identifies host immunity factors associated with disease tolerance., In ecology, “disease tolerance” is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load. To our knowledge, tolerance has to date not been quantified and disentangled from host resistance to disease in any clinically relevant human infection. Using data from the Swiss HIV Cohort Study, we investigated if there is variation in tolerance to HIV in humans and if this variation is associated with polymorphisms in the human genome. In particular, we tested for associations between tolerance and alleles of the Human Leukocyte Antigen (HLA) genes, the CC chemokine receptor 5 (CCR5), the age at which individuals were infected, and their sex. We found that HLA-B alleles associated with better HIV control do not confer tolerance. The slower disease progression associated with these alleles can be fully attributed to the extent of viral load reduction in carriers. However, we observed that tolerance significantly varies across HLA-B genotypes with a relative standard deviation of 34%. Furthermore, we found that HLA-B homozygotes are less tolerant than heterozygotes. Lastly, tolerance was observed to decrease with age, resulting in a 1.7-fold difference in disease progression between 20 and 60-y-old individuals with the same viral load. Thus, disease tolerance is a feature of infection with HIV, and the identification of the mechanisms involved may pave the way to a better understanding of pathogenesis., Author Summary When confronted with pathogens, hosts can either evolve to fight them or learn to live with them. The first of these two strategies is called “resistance” and the second “tolerance”. In the context of HIV, many genes conferring resistance have been identified, but no tolerance genes are known. Using statistical techniques originating from plant ecology, we analyzed data from an HIV cohort to look for differences in tolerance between HIV-infected individuals and tested whether they go hand in hand with genetic differences. We found that younger people are more tolerant to HIV infection. We also observed that individuals who carry two different alleles of HLA-B, an important immunity gene, are more tolerant. These findings add to our understanding of how hosts tolerate infections and could open new avenues for treating infections.
Published: 2014
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35. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

Author: Rotger, M, Glass, Tr, Junier, T, Lundgren, J, Neaton, Jd, Poloni, Es, van 't Wout AB, Lubomirov, R, Colombo, S, Martinez, R, Rauch, A, Günthard, Hf, Neuhaus, J, Wentworth, D, van Manen, D, Gras, La, Schuitemaker, H, Albini, L, Torti, C, Jacobson, Lp, Li, X, Kingsley, La, Carli, F, Guaraldi, G, Ford, Es, Sereti, I, Hadigan, C, Martinez, E, Arnedo, M, Egaña-Gorroño, L, Gatell, Jm, Law, M, Bendall, C, Petoumenos, K, Rockstroh, J, Wasmuth, Jc, Kabamba, K, Delforge, M, De Wit, S, Berger, F, Mauss, S, de Paz Sierra, M, Losso, M, Belloso, Wh, Leyes, M, Campins, A, Mondi, A, De Luca, A, Bernardino, I, Barriuso-Iglesias, M, Torrecilla-Rodriguez, A, Gonzalez-Garcia, J, Arribas, Jr, Fanti, I, Gel, S, Puig, J, Negredo, E, Gutierrez, M, Domingo, P, Fischer, J, Fätkenheuer, G, Alonso-Villaverde, C, Macken, A, Woo, J, Mcginty, T, Mallon, P, Mangili, A, Skinner, S, Wanke, Ca, Reiss, P, Weber, R, Bucher, Hc, Fellay, J, Telenti, A, Tarr, Pe, Vullo, V, Magnificent, Consortium, Insight, Swiss HIV Cohort Study, Mastroianni, C, MAGNIFICENT Consortium, Swiss HIV Cohort Study, INSIGHT, Rotger, M., Glass, TR., Lubomirov, R., Bucher, HC., Telenti, A., Tarr, PE., Junier, T., Poloni, ES., Fellay, J., Colombo, S., Martinez, R., Rauch, A., Weber, R., Günthard, HF., Neuhaus, J., Wentworth, D., Lundgren, J., Neaton, JD., van Manen, D., Gras, AL., Schuitemaker, H., van Wout AB., Reiss, P., Albini, L., Torti, C., Jacobson, LP., Li, X., Kingsley, LA., Carli, F., Guaraldi, G., Ford, ES., Sereti, I., Hadigan, C., Martinez, E., Arnedo-Valero, M., Egaña-Gorroño, L., Gatell, JM., Law, M., Bendall, C., Petoumenos, K., Rockstroh, J., Wasmuth, JC., Kabamba, K., Delforge, M., De Wit, S., Berger, F., Mauss, S., Sierra Mde, P., Losso, M., Belloso, WH., Leyes, M., Campins, A., Mondi, A., De Luca, A., Bernardino, I., Barriuso-Iglesias£££Mónica£££ M., Rodriguez, AT., Garcia, JG., Arribas, JR., Fanti, I., Gel, S., Puig, J., Negredo, E., Gutierrez, M., Domingo, P., Fischer, J., Fätkenheuer, G., Alonso-Villaverde, C., Macken, A., Woo, J., McGinty, T., Mallon, P., Mangili, A., Skinner, S., Wanke, CA., Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Trkola, A., Vernazza, P., Prins, YS., Kuijpers, TW., Scherpbier, HJ., Boer, K., van der Meer JT., Wit, FW., Godfried, MH., van der Poll, T., Nellen, FJ., Lange, JM., Geerlings, SE., van Vugt, M., Vrouenraets, SM., Pajkrt, D., Bos, JC., van der Valk, M., Schreij, G., Lowe, S., Lashof, AO., Pronk, MJ., Bravenboer, B., van der Ende ME., de Vries-Sluijs TE., Schurink, CA., van der Feltz, M., Nouwen, JL., Gelinck, LB., Verbon, A., Rijnders, BJ., van de Ven-de Ruiter ED., Slobbe, L., Haag, D., Kauffmann, RH., Schippers, EF., Groeneveld, PH., Alleman, MA., Bouwhuis, JW., ten Kate RW., Soetekouw, R., Kroon, FP., van den Broek PJ., van Dissel JT., Arend, SM., van Nieuwkoop, C., de Boer MJ., Jolink, H., den Hollander JG., Pogany, K., Bronsveld, W., Kortmann, W., van Twillert, G., van Houte DP., Polée, MB., van Vonderen MG., ten Napel CH., Kootstra, GJ., Brinkman, K., Blok, WL., Frissen, PH., Schouten, WE., van den Berk GE., Juttmann, JR., van Kasteren ME., Brouwer, AE., Mulder, JW., van Gorp EC., Smit, PM., Weijer, S., van Eeden, A., Verhagen, DW., Sprenger, HG., Doedens, R., Scholvinck, EH., van Assen, S., Stek, CJ., Hoepelman, IM., Mudrikova, T., Schneider, MM., Jaspers, CA., Ellerbroek, PM., Peters, EJ., Maarschalk-Ellerbroek, LJ., Oosterheert, JJ., Arends, JE., Wassenberg, MW., van der Hilst JC., Richter, C., van der Berg JP., Gisolf, EH., Margolick, JB., Plankey, M., Crain, B., Dobs, A., Farzadegan, H., Gallant, J., Johnson-Hill, L., Sacktor, N., Selnes, O., Shepard, J., Thio, C., Phair, JP., Wolinsky, SM., Badri, S., Conover, C., O'Gorman, M., Ostrow, D., Palella, F., Ragin, A., Detels, R., Martínez-Maza, O., Aronow, A., Bolan, R., Breen, E., Butch, A., Fahey, J., Jamieson, B., Miller, EN., Oishi, J., Vinters, H., Visscher, BR., Wiley, D., Witt, M., Yang, O., Young, S., Zhang, ZF., Rinaldo, CR., Becker, JT., Cranston, RD., Martinson, JJ., Mellors, JW., Silvestre, AJ., Stall, RD., Muñoz, A., Abraham, A., Althoff, K., Cox, C., D'Souza, G., Gange, SJ., Golub, E., Schollenberger, J., Seaberg, EC., Su, S., Huebner, RE., Dominguez, G., Moroni, M., Angarano, G., Antinori, A., Carosi, G., Cauda, R., Monforte£££A d'Arminio£££ A., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, CF., Sagnelli, E., Viale, PL., Von Schlosser, F., d'Arminio Monforte, A., Ammassari, A., Andreoni, M., Balotta, C., Bonfanti, P., Bonora, S., Borderi, M., Capobianchi, MR., Castagna, A., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Gargiulo, M., Gervasoni, C., Girardi, E., Lichtner, M., Lo Caputo, S., Madeddu, G., Maggiolo, F., Marcotullio, S., Monno, L., Murri, R., Mussini, C., Puoti, M., Formenti, T., Galli, L., Lorenzini, P., Montroni, M., Giacometti, A., Costantini, A., Riva, A., Tirelli, U., Martellotta, F., Ladisa, N., Lazzari, G., Verucchi, G., Castelli, F., Scalzini, A., Minardi, C., Bertelli, D., Quirino, T., Abeli, C., Manconi, PE., Piano, P., Vecchiet, J., Falasca, K., Carnevale, G., Lorenzotti, S., Sighinolfi, L., Segala, D., Leoncini, F., Mazzotta, F., Pozzi, M., Cassola, G., Viscoli, G., Viscoli, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Castelli, P., Rizzardini, G., Ridolfo, AL., Foschi, A., Salpietro, S., Galli, A., Bigoloni, A., Spagnuolo, V., Merli, S., Carenzi, L., Moioli, MC., Cicconi, P., Bisio, L., Gori, A., Lapadula, G., Abrescia, N., Chirianni, A., De Marco, M., Ferrari, C., Borghi, R., Baldelli, F., Belfiori, B., Parruti, G., Ursini, T., Magnani, G., Ursitti, MA., Narciso, P., Tozzi, V., Vullo, V., d'Avino, A., Zaccarelli, M., Gallo, L., Acinapura, R., Capozzi, M., Libertone, R., Trotta, MP., Tebano, G., Cattelan, AM., Mura, MS., Caramello, P., Orofino, GC., Sciandra, M., Raise, Ebo, F., Pellizzer, G., Manfrin, V., McManus, H., Wright, S., Moore, R., Edwards, S., Medische Microbiologie, RS: CAPHRI School for Public Health and Primary Care, AII - Amsterdam institute for Infection and Immunity, Experimental Immunology, Other departments, Graduate School, APH - Amsterdam Public Health, Global Health, Medical Microbiology and Infection Prevention, Paediatric Infectious Diseases / Rheumatology / Immunology, Other Research, Obstetrics and Gynaecology, Infectious diseases, General Internal Medicine, Center of Experimental and Molecular Medicine, University of Zurich, Tarr, Philip E, Rotger, M, Glass, T, Junier, T, Lundgren, J, Neaton, J, Poloni, E, Van 'T Wout, A, Lubomirov, R, Colombo, S, Martinez, R, Rauch, A, Günthard, H, Neuhaus, J, Wentworth, D, Van Manen, D, Gras, L, Schuitemaker, H, Albini, L, Torti, C, Jacobson, L, Li, X, Kingsley, L, Carli, F, Guaraldi, G, Ford, E, Sereti, I, Hadigan, C, Martinez, E, Arnedo, M, Egaña Gorroño, L, Gatell, J, Law, M, Bendall, C, Petoumenos, K, Rockstroh, J, Wasmuth, J, Kabamba, K, Delforge, M, De Wit, S, Berger, F, Mauss, S, De Paz Sierra, M, Losso, M, Belloso, W, Leyes, M, Campins, A, Mondi, A, De Luca, A, Bernardino, I, Barriuso Iglesias, M, Torrecilla Rodriguez, A, Gonzalez Garcia, J, Arribas, J, Fanti, I, Gel, S, Puig, J, Negredo, E, Gutierrez, M, Domingo, P, Fischer, J, Fätkenheuer, G, Alonso Villaverde, C, Macken, A, Woo, J, Mcginty, T, Mallon, P, Mangili, A, Skinner, S, Wanke, C, Reiss, P, Weber, R, Bucher, H, Fellay, J, Telenti, A, Tarr, P, Gori, A, Junier, Thomas, Poloni, Estella S., Rotger, Margalida, Glass, Tracy R., Junier, Thoma, Lundgren, Jen, Neaton, James D., Van 't Wout, Angã©lique B., Lubomirov, Rubin, Colombo, Sara, Martinez, Raquel, Rauch, Andri, Gã¼nthard, Huldrych F., Neuhaus, Jacqueline, Wentworth, Deborah, Van Manen, Danielle, Gras, Luuk A., Schuitemaker, Hanneke, Albini, Laura, Torti, Carlo, Jacobson, Lisa P., Li, Xiuhong, Kingsley, Lawrence A., Carli, Federica, Guaraldi, Giovanni, Ford, Emily S., Sereti, Irini, Hadigan, Colleen, Martinez, Esteban, Arnedo, Mireia, Egaã±a gorroã±o, Lander, Gatell, Jose M., Law, Matthew, Bendall, Courtney, Petoumenos, Kathy, Rockstroh, Jã¼rgen, Wasmuth, Jan christian, Kabamba, Kabeya, Delforge, Marc, De Wit, Stephane, Berger, Florian, Mauss, Stefan, De Paz Sierra, Mariana, Losso, Marcelo, Belloso, Waldo H., Leyes, Maria, Campins, Antoni, Mondi, Annalisa, De Luca, Andrea, Bernardino, Ignacio, Barriuso iglesias, Mã³nica, Torrecilla rodriguez, Ana, Gonzalez garcia, Juan, Arribas, Josã© R., Fanti, Iuri, Gel, Silvia, Puig, Jordi, Negredo, Eugenia, Gutierrez, Mar, Domingo, Pere, Fischer, Julia, Fã¤tkenheuer, Gerd, Alonso villaverde, Carlo, Macken, Alan, Woo, Jame, Mcginty, Tara, Mallon, Patrick, Mangili, Alexandra, Skinner, Sally, Wanke, Christine A., Reiss, Peter, Weber, Rainer, Bucher, Heiner C., Fellay, Jacque, Telenti, Amalio, Tarr, Philip E. Swiss Hiv Cohort, and Castagna, Antonella
Subjects: Male, HIV Infections, Genome-wide association study, 030204 cardiovascular system & hematology, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, Coronary artery disease, 0302 clinical medicine, ddc:590, Risk Factors, Abacavir, 80 and over, genetics, 030212 general & internal medicine, Family history, Articles and Commentaries, Aged, 80 and over, education.field_of_study, medicine.diagnostic_test, traditional risk factor, Single Nucleotide, Middle Aged, 3. Good health, Infectious Diseases, traditional risk factors, Cohort, Female, HIV infection, antiretroviral therapy, coronary artery disease, Human, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Adolescent, Population, Infectious Disease, 610 Medicine & health, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Aged, Coronary Artery Disease, Humans, Polymorphism, Young Adult, 03 medical and health sciences, Internal medicine, medicine, education, Genetic testing, business.industry, Risk Factor, 2725 Infectious Diseases, Odds ratio, medicine.disease, Immunology, genetic, business
Abstract: BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.
Published: 2013
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36. Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs

Author: Oberle Corinna S, Joos Beda, Rusert Peter, Campbell Nottania K, Beauparlant David, Kuster Herbert, Weber Jacqueline, Schenkel Corinne D, Scherrer Alexandra U, Magnus Carsten, Kouyos Roger, Rieder Philip, Niederöst Barbara, Braun Dominique L, Pavlovic Jovan, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Trkola Alexandra, Metzner Karin J, Günthard Huldrych F, Swiss HIV Cohort Study (SHCS), Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Braun, D., Bucher, H., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rudin, C., Schöni-Affolter, F., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Günthard, Huldrych F
Subjects: 10028 Institute of Medical Virology, 0301 basic medicine, Male, viruses, HIV Infections, Neutralization, law.invention, 10234 Clinic for Infectious Diseases, Env Gene Products, law, Leukocytes, ddc:616, education.field_of_study, Replicative capacity, env Gene Products, Human Immunodeficiency Virus, Reply to Correspondence, Neutralizing/blood/immunology, Homosexuality, Phenotype, 3. Good health, Infectious Diseases, Transmission (mechanics), Acute Disease, Female, Antibody, Mononuclear/drug effects/virology, Sequence Analysis, Population, Entry, 610 Medicine & health, Biology, Antibodies, Neutralizing/blood, Antibodies, Neutralizing/immunology, Genetic Variation, HIV Infections/transmission, HIV Infections/virology, HIV-1/genetics, HIV-1/isolation & purification, HIV-1/physiology, Homosexuality, Male, Humans, Interferon-alpha/pharmacology, Leukocytes, Mononuclear/drug effects, Leukocytes, Mononuclear/virology, Neutralization Tests, Sequence Analysis, DNA, Stochastic Processes, Viral Tropism, Virus Internalization, env Gene Products, Human Immunodeficiency Virus/genetics, env Gene Products, Human Immunodeficiency Virus/immunology, Virus, Antibodies, 03 medical and health sciences, HIV-1, Transmission, Envelope, IFNalpha, Virology, education, Human Immunodeficiency Virus/genetics/immunology, Genetic diversity, HIV-1/genetics/isolation & purification/physiology, Host (biology), Research, Interferon-alpha, 2725 Infectious Diseases, HIV Infections/transmission/virology, DNA, Antibodies, Neutralizing, 030104 developmental biology, 2406 Virology, Leukocytes, Mononuclear, biology.protein, IFNα
Abstract: Background Mucosal HIV-1 transmission predominantly results in a single transmitted/founder (T/F) virus establishing infection in the new host despite the generally high genetic diversity of the transmitter virus population. To what extent HIV-1 transmission is a stochastic process or driven by selective forces that allow T/F viruses best to overcome bottlenecks in transmission has not been conclusively resolved. Building on prior investigations that suggest HIV-1 envelope (Env) features to contribute in the selection process during transmission, we compared phenotypic virus characteristics of nine HIV-1 subtype B transmission pairs, six men who have sex with men and three male-to-female transmission pairs. Results All recipients were identified early in acute infection and harbored based on extensive sequencing analysis a single T/F virus allowing a controlled analysis of virus properties in matched transmission pairs. Recipient and transmitter viruses from the closest time point to transmission showed no signs of selection for specific Env modifications such as variable loop length and glycosylation. Recipient viruses were resistant to circulating plasma antibodies of the transmitter and also showed no altered sensitivity to a large panel of entry inhibitors and neutralizing antibodies. The recipient virus did not consistently differ from the transmitter virus in terms of entry kinetics, cell–cell transmission and replicative capacity in primary cells. Our paired analysis revealed a higher sensitivity of several recipient virus isolates to interferon-α (IFNα) which suggests that resistance to IFNα cannot be a general driving force in T/F establishment. Conclusions With the exception of increased IFNα sensitivity, none of the phenotypic virus properties we investigated clearly distinguished T/F viruses from their matched transmitter viruses supporting the notion that at least in subtype B infection HIV-1 transmission is to a considerable extent stochastic. Electronic supplementary material The online version of this article (doi:10.1186/s12977-016-0299-0) contains supplementary material, which is available to authorized users.
Published: 2016
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37. Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients

Author: Alexandra U Scherrer, Bruno Ledergerber, Viktor von Wyl, Jürg Böni, Sabine Yerly, Thomas Klimkait, Cristina Cellerai, Hansjakob Furrer, Alexandra Calmy, Matthias Cavassini, Luigia Elzi, Pietro L Vernazza, Enos Bernasconi, Huldrych F Günthard, Swiss HIV Cohort Study, University of Zurich, Swiss HIV Cohort Study, Remy, B., Rickenbach, M., Schöni-Affolter, F., Vallet, Y., Francioli, MC., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Rudin, C., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Male, 10028 Institute of Medical Virology, lcsh:Medicine, HIV Infections, medicine.disease_cause, Gastroenterology, Nucleoside Reverse Transcriptase Inhibitor, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, HIV Protease, HIV Protease Inhibitor, 030212 general & internal medicine, lcsh:Science, ddc:616, 0303 health sciences, Mutation, Multidisciplinary, Hazard ratio, HIV diagnosis and management, Viral Load, 3. Good health, HIV epidemiology, Cohort, RNA, Viral, Medicine, Infectious diseases, HIV clinical manifestations, Female, Viral load, Research Article, medicine.medical_specialty, Retrovirology and HIV immunopathogenesis, Sexually Transmitted Diseases, 610 Medicine & health, Viral diseases, 1100 General Agricultural and Biological Sciences, Biology, 03 medical and health sciences, CD4 Lymphocyte Count, Drug Resistance, Viral/genetics, HIV Infections/drug therapy, HIV Infections/virology, HIV Protease/genetics, HIV Protease Inhibitors/pharmacology, HIV Protease Inhibitors/therapeutic use, Humans, RNA, Viral/blood, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Drug Resistance, Viral, medicine, Genetics, HIV Protease Inhibitors/pharmacology/therapeutic use, Protease inhibitor (pharmacology), HIV Infections/drug therapy/virology, 030304 developmental biology, Evolutionary Biology, 1000 Multidisciplinary, Population Biology, Proportional hazards model, lcsh:R, Computational Biology, HIV, HIV Protease Inhibitors, Immunology, Genetic Polymorphism, 570 Life sciences, biology, lcsh:Q, Population Genetics
Abstract: Background Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naive patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. Methods To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. Results We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0–1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5–1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. Conclusions The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.
Published: 2012
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38. Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy

Author: Bernard Hirschel, Chantal Csajka, Enos Bernasconi, Margalida Rotger, Laurent A. Decosterd, Huldrych F. Günthard, Amalio Telenti, Martin Rickenbach, Catia Marzolini, Dunja Nicca, Heiner C. Bucher, Tracy R. Glass, Gilles Wandeler, Manuel Battegay, University of Zurich, Marzolini, Catia, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, C., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, Ch., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Male, Viral Diseases, Time Factors, Adult, Anti-HIV Agents/pharmacology, Anti-HIV Agents/therapeutic use, HIV Infections/drug therapy, HIV Infections/genetics, HIV-1/drug effects, Humans, Logistic Models, Longitudinal Studies, Middle Aged, Patient Compliance/statistics & numerical data, Self Report, HIV Infections, 10234 Clinic for Infectious Diseases, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, Lopinavir, Multidrug Resistance-Associated Protein 2, 3. Good health, Infectious Diseases, Medicine, medicine.drug, Research Article, medicine.medical_specialty, Drugs and Devices, Efavirenz, Anti-HIV Agents, Science, Population, 610 Medicine & health, Single-nucleotide polymorphism, 1100 General Agricultural and Biological Sciences, Microbiology, 03 medical and health sciences, Pharmacotherapy, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Virology, medicine, education, Biology, Clinical Genetics, 1000 Multidisciplinary, 030306 microbiology, business.industry, Odds ratio, Confidence interval, chemistry, Immunology, biology.protein, HIV-1, Patient Compliance, SLCO1B1, business
Abstract: BackgroundGood adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels.MethodsEligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA ResultsFrom January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01-0.99; LPV/r: OR 0.29, 95% CI: 0.09-0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62-18.75; LPV/r: OR 5.65, 95% CI: 1.82-17.56).ConclusionsThe investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.
Published: 2012
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39. Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations

Author: von Wyl, Viktor, Yerly, Sabine, Böni, Jürg, Shah, Cyril, Cellerai, Cristina, Klimkait, Thomas, Battegay, Manuel, Bernasconi, Enos, Cavassini, Matthias, Furrer, Hansjakob, Hirschel, Bernard, Vernazza, Pietro L, Ledergerber, Bruno, Günthard, Huldrych F, Swiss HIV Cohort, Study, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Müller, N., Nadal, D., Pantaleo, C., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., von Wyl, V., Weber, R., Yerly, S., University of Zurich, and von Wyl, V
Subjects: Oncology, 10028 Institute of Medical Virology, Male, Human immunodeficiency virus (HIV), HIV Infections, Drug resistance, medicine.disease_cause, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, ddc:616, 0303 health sciences, Incidence, Lamivudine, virus diseases, Lopinavir, Middle Aged, Viral Load, 3. Good health, HIV-1/classification/drug effects/genetics/isolation & purification, Infectious Diseases, Treatment Outcome, Female, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Efavirenz, Genotype, Anti-HIV Agents, 610 Medicine & health, Emtricitabine, 03 medical and health sciences, Zidovudine, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/pharmacology, Drug Resistance, Viral, HIV Infections/drug therapy, HIV Infections/virology, HIV-1/classification, HIV-1/drug effects, Humans, Internal medicine, medicine, Antiretroviral treatment, HIV Infections/drug therapy/virology, 030306 microbiology, business.industry, Anti-HIV Agents/administration & dosage/pharmacology, 2725 Infectious Diseases, chemistry, Immunology, HIV-1, 570 Life sciences, biology, business
Abstract: BACKGROUND: Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence. METHODS: Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range). RESULTS: Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (500 copies/mL). CONCLUSIONS: The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resistance emergence, most likely because of improved tolerability and pharmacokinetics resulting from a once-daily dosage.
Published: 2012
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40. Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic

Author: Wandeler, Gilles, Gsponer, Thomas, Bregenzer, Andrea, Günthard, Huldrych F, Clerc, Olivier, Calmy, Alexandra, Stöckle, Marcel, Bernasconi, Enos, Furrer, Hansjakob, Rauch, Andri, Swiss HIV Cohort Study, University of Zurich, Wandeler, Gilles, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dubs, R., Egger, M., Elzi, L., Fehr, J., Fischer, M., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., and von Wyl, V.
Subjects: Male, HIV Infections, Hepatitis C/epidemiology/virology, medicine.disease_cause, 2726 Microbiology (medical), Men who have sex with men, Serology, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, Switzerland/epidemiology, Risk Factors, 030212 general & internal medicine, Substance Abuse, Intravenous, 610 Medicine & health, ddc:616, Incidence (epidemiology), Incidence, virus diseases, Hepatitis C, HIV Infections/epidemiology/virology, 3. Good health, Infectious Diseases, 030211 gastroenterology & hepatology, Female, Switzerland, Cohort study, Microbiology (medical), Adult, Hepatitis C virus, Substance Abuse, Intravenous/epidemiology/virology, Statistics, Nonparametric, 03 medical and health sciences, medicine, Humans, Homosexuality, Male, Seroconversion, Epidemics, Chi-Square Distribution, business.industry, 2725 Infectious Diseases, medicine.disease, Virology, digestive system diseases, Homosexuality, Male/statistics & numerical data, Immunology, Syphilis, business
Abstract: BACKGROUND: Hepatitis C virus (HCV) infection has a growing impact on morbidity and mortality in patients infected with human immunodeficiency virus (HIV). We assessed trends in HCV incidence in the different HIV transmission groups in the Swiss HIV Cohort Study (SHCS). METHODS: HCV infection incidence was assessed from 1998, when routine serial HCV screening was introduced in the SHCS, until 2011. All HCV-seronegative patients with at least 1 follow-up serology were included. Incidence rates (IRs) of HCV infections were compared between men who have sex with men (MSM), injection drug users (IDU), and heterosexuals (HET). RESULTS: HCV incidence was assessed in 3333 MSM, 123 IDU, and 3078 HET with a negative HCV serology at baseline. Over 23 707 person-years (py) for MSM, 733 py for IDU, and 20 752 py for HET, 101 (3%), 41 (33%), and 25 (1%) of patients seroconverted, respectively. The IR of HCV infections in MSM increased from 0.23 (95% credible interval [CrI], .08-.54) per 100 py in 1998 to 4.09 (95% CrI, 2.57-6.18) in 2011. The IR decreased in IDU and remained
Published: 2012
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41. Influence of antiretroviral therapy on liver disease

Author: Rainer Weber, Helen Kovari, University of Zurich, and Kovari, H
Subjects: medicine.medical_specialty, Anti-HIV Agents, Immunology, 2720 Hematology, 610 Medicine & health, HIV Infections, Disease, 10234 Clinic for Infectious Diseases, Liver disease, Virology, Antiretroviral Therapy, Highly Active, medicine, Humans, Intensive care medicine, 2403 Immunology, Oncology (nursing), business.industry, Hematology, 2725 Infectious Diseases, medicine.disease, Hepatitis B, Antiretroviral therapy, Hepatitis C, Infectious Diseases, Oncology, 2406 Virology, 2730 Oncology, business, 2917 Oncology (nursing)
Abstract: Liver disease is a major cause of morbidity and mortality in HIV-infected persons. The long-term beneficial versus potentially harmful influence of antiretroviral therapy (ART) on the liver is debated. We review current data on factors contributing to liver disease in HIV-monoinfected as well as in HIV/viral hepatitis-coinfected patients, highlighting the role of ART, HIV itself, immunodeficiency, patient characteristics, and lifestyle risk factors.New ART-related clinical syndromes, including noncirrhotic portal hypertension and nonalcoholic fatty liver disease, have emerged, and observational data suggest long-term ART-associated liver injury. Recently, there is increasing evidence that HIV itself and immunosuppression are contributing to liver injury in both HIV-coinfected and HIV-monoinfected patients. In HIV-positive persons, ART attenuates progression of chronic viral hepatitis.Current expert guidelines recommend earlier treatment of HIV infection in persons coinfected with hepatitis B virus and possibly hepatitis C virus. It is unknown whether an earlier start of ART is beneficial for the liver in HIV-monoinfected patients. Future research should focus on long-term ART-related hepatotoxicity.
Published: 2011

42. A comparison of initial antiretroviral therapy in the Swiss HIV Cohort Study and the recommendations of the International AIDS Society-USA

Author: Gilles Wandeler, Olivia Keiser, Bernard Hirschel, Huldrych F Günthard, Enos Bernasconi, Manuel Battegay, Olivier Clerc, Pietro L Vernazza, Hansjakob Furrer, Swiss HIV Cohort Study, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dubs, R., Egger, M., Elzi, L., Fehr, J., Fischer, M., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Kaiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Tejada, BM., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., Wyl, V., University of Zurich, and Wandeler, G
Subjects: Male, Pediatrics, Time Factors, Epidemiology, Organizations, Nonprofit, Treatment outcome, Adolescent, Adult, Anti-HIV Agents/therapeutic use, Cohort Studies, Demography, Drug Prescriptions/statistics & numerical data, Female, Guideline Adherence/statistics & numerical data, HIV Infections/drug therapy, Humans, Middle Aged, Switzerland, Treatment Outcome, Young Adult, Human immunodeficiency virus (HIV), lcsh:Medicine, HIV Infections, medicine.disease_cause, 01 natural sciences, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Clinical Epidemiology, 030212 general & internal medicine, Young adult, lcsh:Science, Multidisciplinary, HIV diagnosis and management, Antivirals, Viral Persistence and Latency, 3. Good health, HIV epidemiology, Medicine, Infectious diseases, Guideline Adherence, Viral load, Research Article, Cohort study, Drugs and Devices, medicine.medical_specialty, Infectious Disease Control, Clinical Research Design, Anti-HIV Agents, 610 Medicine & health, Viral diseases, 1100 General Agricultural and Biological Sciences, Microbiology, Drug Prescriptions, Infectious Disease Epidemiology, 03 medical and health sciences, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), 1300 General Biochemistry, Genetics and Molecular Biology, Virology, medicine, 0101 mathematics, Biology, 1000 Multidisciplinary, business.industry, 010102 general mathematics, lcsh:R, HIV, medicine.disease, Antiretroviral therapy, Family medicine, lcsh:Q, business
Abstract: BACKGROUND: In order to facilitate and improve the use of antiretroviral therapy (ART), international recommendations are released and updated regularly. We aimed to study if adherence to the recommendations is associated with better treatment outcomes in the Swiss HIV Cohort Study (SHCS). METHODS: Initial ART regimens prescribed to participants between 1998 and 2007 were classified according to IAS-USA recommendations. Baseline characteristics of patients who received regimens in violation with these recommendations (violation ART) were compared to other patients. Multivariable logistic and linear regression analyses were performed to identify associations between violation ART and (i) virological suppression and (ii) CD4 cell count increase, after one year. RESULTS: Between 1998 and 2007, 4189 SHCS participants started 241 different ART regimens. A violation ART was started in 5% of patients. Female patients (adjusted odds ratio aOR 1.83, 95%CI 1.28-2.62), those with a high education level (aOR 1.49, 95%CI 1.07-2.06) or a high CD4 count (aOR 1.53, 95%CI 1.02-2.30) were more likely to receive violation ART. The proportion of patients with an undetectable viral load (
Published: 2011
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43. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study

Author: Hasse, Barbara, Ledergerber, Bruno, Furrer, Hansjakob, Battegay, Manuel, Hirschel, Bernhard, Cavassini, Matthias, Bertisch, Barbara, Bernasconi, Enos, Weber, Rainer, Swiss HIV Cohort Study, University of Zurich, Hasse, B, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dubs, R., Egger, M., Elzi, L., Fehr, J., Fischer, M., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Telenti, A., Trkola, A., von Vernazza, P., Wyl, V., Weber, R., and Yerly, S.
Subjects: Microbiology (medical), Adult, Male, medicine.medical_specialty, Aging, Osteoporosis, HIV Infections, 610 Medicine & health, Comorbidity, 2726 Microbiology (medical), Cohort Studies, 10234 Clinic for Infectious Diseases, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Diabetes mellitus, Surveys and Questionnaires, medicine, Humans, Myocardial infarction, Prospective Studies, Stroke, Aged, business.industry, Hazard ratio, 2725 Infectious Diseases, Middle Aged, Viral Load, medicine.disease, Surgery, CD4 Lymphocyte Count, Infectious Diseases, Female, business, Switzerland, HIV Infections/complications, HIV Infections/epidemiology, Questionnaires, Switzerland/epidemiology, Cohort study
Abstract: BACKGROUND: Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study. METHODS: The Swiss HIV Cohort Study is a prospective observational cohort established in 1988 with continuous enrollment. We determined the incidence of clinical events (per 1000 person-years) from January 2008 (when a new questionnaire on non-AIDS-related morbidity was introduced) through December 2010. Differences across age groups were analyzed using Cox regression, adjusted for CD4 cell count, viral load, sex, injection drug use, smoking, and years of HIV infection. RESULTS: Overall, 8444 (96%) of 8848 participants contributed data from 40,720 semiannual visits; 2233 individuals (26.4%) were aged 50-64 years, and 450 (5.3%) were aged ≥65 years. The median duration of HIV infection was 15.4 years (95% confidence interval [CI], 9.59-22.0 years); 23.2% had prior clinical AIDS. We observed 994 incident non-AIDS events in the reference period: 201 cases of bacterial pneumonia, 55 myocardial infarctions, 39 strokes, 70 cases of diabetes mellitus, 123 trauma-associated fractures, 37 fractures without adequate trauma, and 115 non-AIDS malignancies. Multivariable hazard ratios for stroke (17.7; CI, 7.06-44.5), myocardial infarction (5.89; 95% CI, 2.17-16.0), diabetes mellitus (3.75; 95% CI, 1.80-7.85), bone fractures without adequate trauma (10.5; 95% CI, 3.58-30.5), osteoporosis (9.13; 95% CI, 4.10-20.3), and non-AIDS-defining malignancies (6.88; 95% CI, 3.89-12.2) were elevated for persons aged ≥65 years. CONCLUSIONS: Comorbidity and multimorbidity because of non-AIDS diseases, particularly diabetes mellitus, cardiovascular disease, non-AIDS-defining malignancies, and osteoporosis, become more important in care of HIV-infected persons and increase with older age.
Published: 2011
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44. The role of migration and domestic transmission in the spread of HIV-1 non-B subtypes in Switzerland

Author: von Wyl, Viktor, Kouyos, Roger D, Yerly, Sabine, Böni, Jürg, Shah, Cyril, Bürgisser, Philippe, Klimkait, Thomas, Weber, Rainer, Hirschel, Bernard, Cavassini, Matthias, Staehelin, Cornelia, Battegay, Manuel, Vernazza, Pietro L, Bernasconi, Enos, Ledergerber, Bruno, Bonhoeffer, Sebastian, Günthard, Huldrych F, Swiss HIV Cohort Study, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, H., Bu, P., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dubs, R., Egger, M., Elzi, L., Fehr, J., Fischer, M., Flepp, M., Francioli, P., Furrer, H., Fux, C., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, H., Hirschel, B., Ho, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., von Wyl, V., Weber, R., Yerly, S., University of Zurich, and von Wyl, V
Subjects: 10028 Institute of Medical Virology, Male, viruses, Immigration, Ethnic group, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, law.invention, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, law, Prevalence, Immunology and Allergy, Medicine, Cluster Analysis, 030212 general & internal medicine, health care economics and organizations, media_common, ddc:616, 0303 health sciences, Likelihood Functions, High prevalence, virus diseases, Emigration and Immigration, humanities, 3. Good health, Infectious Diseases, Transmission (mechanics), 2723 Immunology and Allergy, Female, Switzerland, Cohort study, Maximum likelihood, media_common.quotation_subject, education, Molecular Sequence Data, Black People, Gene Products, pol, 610 Medicine & health, White People, 03 medical and health sciences, Asian People, Humans, Homosexuality, Male, Heterosexuality, 030304 developmental biology, African Continental Ancestry Group/statistics & numerical data, Asian Continental Ancestry Group/statistics & numerical data, European Continental Ancestry Group/statistics & numerical data, Gene Products, pol/metabolism, HIV Infections/ethnology, HIV Infections/genetics, HIV-1/genetics, HIV-1/metabolism, Heterosexuality/statistics & numerical data, Homosexuality, Male/statistics & numerical data, Logistic Models, Switzerland/epidemiology, business.industry, 2725 Infectious Diseases, HIV-1, 570 Life sciences, biology, business, Demography
Abstract: The Journal of Infectious Diseases, 204 (7), ISSN:0022-1899, ISSN:1537-6613
Published: 2011
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45. Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study

Author: Séverine Louvel, Gladys Martinetti, Enos Bernasconi, Pietro Vernazza, Huldrych F. Günthard, Heiner C. Bucher, Hans H. Hirsch, Jan Fehr, Thomas Klimkait, Sabine Yerly, Christoph A Fux, Viktor von Wyl, Manuel Battegay, Bernard Hirschel, François Hamy, Philippe Bürgisser, Tracey R. Glass, Matthias Cavassini, Jürg Böni, University of Zurich, Klimkait, T, Swiss HIV Cohort Study, Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Calmy, A., Cattacin, S., Cavassini, M., Dubs, R., Egger, M., Elzi, L., Fehr, J., Fischer, M., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, HF., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Müller, N., Nadal, D., Paccaud, F., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., de Tejada BM., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., von Wyl, V., Weber, R., and Yerly, S.
Subjects: Oncology, 10028 Institute of Medical Virology, Male, Multivariate analysis, viruses, lcsh:Medicine, HIV Infections, Virus Replication, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, Genotype, 030212 general & internal medicine, Virus Replication/drug effects/physiology, Medicine(all), ddc:616, 0303 health sciences, Adult, Anti-HIV Agents/pharmacology, Anti-HIV Agents/therapeutic use, Dose-Response Relationship, Drug, Drug Resistance, Viral/physiology, Female, HIV Infections/diagnosis, HIV Infections/drug therapy, HIV-1/physiology, Humans, Microbial Sensitivity Tests/methods, Middle Aged, Phenotype, Predictive Value of Tests, Prognosis, Switzerland, Virus Replication/drug effects, Virus Replication/physiology, General Medicine, HIV Infections/diagnosis/drug therapy/virology, 3. Good health, Predictive value of tests, Cohort study, medicine.medical_specialty, Anti-HIV Agents, 610 Medicine & health, Microbial Sensitivity Tests, General Biochemistry, Genetics and Molecular Biology, Virus, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Drug Resistance, Viral, medicine, Anti-HIV Agents/pharmacology/therapeutic use, 030304 developmental biology, Biochemistry, Genetics and Molecular Biology(all), business.industry, Research, lcsh:R, Odds ratio, Institutional repository, Viral replication, Immunology, HIV-1, 570 Life sciences, biology, business
Abstract: Background Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Methods Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA Results Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). Conclusions In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.
Published: 2010
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46. Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis b or c virus co-infection

Author: Pietro Vernazza, Enos Bernasconi, Andri Rauch, Alain Kenfak Foguena, Bruno Ledergerber, Manuel Battegay, Rainer Weber, Bernard Hirschel, Helen Kovari, Nicolas J. Mueller, University of Zurich, and Kovari, H
Subjects: Male, viruses, HIV Infections, medicine.disease_cause, Rate ratio, Gastroenterology, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, Risk Factors, Longitudinal Studies, Poisson Distribution, Prospective Studies, ddc:616, biology, Stavudine, Alanine Transaminase, Alcohol Drinking/metabolism, Hepatitis B, Middle Aged, Viral Load, Hepatitis C, Infectious Diseases, Anti-Retroviral Agents, Liver, Coinfection, Female, Hepatitis C/enzymology/virology, Viral load, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Alcohol Drinking, Hepatitis C virus, 610 Medicine & health, Human-Immunodeficiency-Virus, Fatty Liver-Disease, Antiretroviral Therapy, Diabetes-Mellitus, United-States, Steatosis, Prevalence, Toxicity, Cohort, Hepatotoxicity, Sensitivity and Specificity, Internal medicine, medicine, Humans, Hepatitis B/enzymology/virology, Hepatitis B virus, business.industry, Liver/enzymology, 2725 Infectious Diseases, HIV Infections/drug therapy/ enzymology/virology, medicine.disease, Anti-Retroviral Agents/adverse effects/therapeutic use, Alanine transaminase, Immunology, Multivariate Analysis, biology.protein, Alanine Transaminase/blood/ metabolism, business
Abstract: BACKGROUND: Chronic liver disease in human immunodeficiency virus (HIV)-infected patients is mostly caused by hepatitis virus co-infection. Other reasons for chronic alanine aminotransferase (ALT) elevation are more difficult to diagnose. METHODS: We studied the incidence of and risk factors for chronic elevation of ALT levels (greater than the upper limit of normal at 2 consecutive semi-annual visits) in participants of the Swiss HIV Cohort Study without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who were seen during the period 2002-2008. Poisson regression analysis was used. RESULTS: A total of 2365 participants were followed up for 9972 person-years (median age, 38 years; male sex, 66%; median CD4+ cell count, 426/microL; receipt of antiretroviral therapy [ART], 56%). A total of 385 participants (16%) developed chronic elevated ALT levels, with an incidence of 3.9 cases per 100 person-years (95% confidence interval [CI], 3.5-4.3 cases per 100 person-years). In multivariable analysis, chronic elevated ALT levels were associated with HIV RNA level >100,000 copies/mL (incidence rate ratio [IRR], 2.23; 95% CI, 1.45-3.43), increased body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) (BMI of 25-29.9 was associated with an IRR of 1.56 [95% CI, 1.24-1.96]; a BMI 30 was associated with an IRR of 1.70 [95% CI, 1.16-2.51]), severe alcohol use (1.83 [1.19-2.80]), exposure to stavudine (IRR per year exposure, 1.12 [95% CI, 1.07-1.17]) and zidovudine (IRR per years of exposure, 1.04 [95% CI, 1.00-1.08]). Associations with cumulative exposure to combination ART, nucleoside reverse-transcriptase inhibitors, and unboosted protease inhibitors did not remain statistically significant after adjustment for exposure to stavudine. Black ethnicity was inversely correlated (IRR, 0.52 [95% CI, 0.33-0.82]). Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels. CONCLUSIONS: Among patients without hepatitis virus co-infection, the incidence of chronic elevated ALT levels was 3.9 cases per 100 person-years, which was associated with high HIV RNA levels, increased BMI, severe alcohol use, and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.
Published: 2010
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47. Pulmonary toxoplasmosis, a rare but severe manifestation of a common opportunistic infection in late HIV presenters: report of two cases

Author: A. Schweiger, C. Ebnöther, N. Berther, Huldrych F. Günthard, Herbert Kuster, Helen Kovari, University of Zurich, and Kovari, H
Subjects: Adult, Lung Diseases, Male, Microbiology (medical), 10078 Institute of Parasitology, Pediatrics, medicine.medical_specialty, Opportunistic infection, Antiprotozoal Agents, Human immunodeficiency virus (HIV), Case Report, HIV Infections, 610 Medicine & health, Pneumocystis Jirovecii, medicine.disease_cause, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, 600 Technology, Pulmonary toxoplasmosis, Pneumocystosis, Humans, Medicine, Tomography, Atovaquone, Pneumocystis Pneumonia, Microscopy, AIDS-Related Opportunistic Infections, business.industry, virus diseases, General Medicine, 2725 Infectious Diseases, medicine.disease, Antiretroviral therapy, Toxoplasmosis, CD4 Lymphocyte Count, Pneumonia, Pyrimethamine, Treatment Outcome, Infectious Diseases, Immunology, RNA, Viral, 570 Life sciences, biology, Radiography, Thoracic, Differential diagnosis, business, Bronchoalveolar Lavage Fluid
Abstract: Pulmonary toxoplasmosis is rare, particularly in the era of highly active antiretroviral therapy (HAART). Here, we describe two severe cases in patients not known to be HIV-infected. In both patients, early diagnosis and therapy led to a favourable outcome. Pulmonary toxoplasmosis should be considered in the differential diagnosis in potentially HIV-infected patients with respiratory symptoms
Published: 2010
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48. Adherence as a Predictor of the Development of Class-Specific Resistance Mutations: The Swiss HIV Cohort Study

Author: Dunja Nicca, Alexandra Calmy, Viktor von Wyl, Sabine Yerly, Hansjakob Furrer, Jürg Böni, Heiner C. Bucher, Tracy R. Glass, Huldrych F. Günthard, Matthias Cavassini, Vincent Aubert, Thomas Klimkait, Enos Bernasconi, Swiss HIV Cohort Study, Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Staehelin, C., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., and University of Zurich
Subjects: Adult, Male, medicine.medical_specialty, Genotype, lcsh:Medicine, 610 Medicine & health, Kaplan-Meier Estimate, 1100 General Agricultural and Biological Sciences, Drug resistance, Logistic regression, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Drug Resistance, Viral, medicine, Humans, 030212 general & internal medicine, lcsh:Science, ddc:616, 1000 Multidisciplinary, 0303 health sciences, Multidisciplinary, 030306 microbiology, business.industry, lcsh:R, Odds ratio, Middle Aged, Resistance mutation, Confidence interval, 3. Good health, Regimen, Logistic Models, Anti-Retroviral Agents, Mutation, Immunology, Female, lcsh:Q, business, Research Article, Cohort study
Abstract: Background Non-adherence is one of the strongest predictors of therapeutic failure in HIV-positive patients. Virologic failure with subsequent emergence of resistance reduces future treatment options and long-term clinical success. Methods Prospective observational cohort study including patients starting new class of antiretroviral therapy (ART) between 2003 and 2010. Participants were naïve to ART class and completed ≥1 adherence questionnaire prior to resistance testing. Outcomes were development of any IAS-USA, class-specific, or M184V mutations. Associations between adherence and resistance were estimated using logistic regression models stratified by ART class. Results Of 314 included individuals, 162 started NNRTI and 152 a PI/r regimen. Adherence was similar between groups with 85% reporting adherence ≥95%. Number of new mutations increased with increasing non-adherence. In NNRTI group, multivariable models indicated a significant linear association in odds of developing IAS-USA (odds ratio (OR) 1.66, 95% confidence interval (CI): 1.04-2.67) or class-specific (OR 1.65, 95% CI: 1.00-2.70) mutations. Levels of drug resistance were considerably lower in PI/r group and adherence was only significantly associated with M184V mutations (OR 8.38, 95% CI: 1.26-55.70). Adherence was significantly associated with HIV RNA in PI/r but not NNRTI regimens. Conclusion Therapies containing PI/r appear more forgiving to incomplete adherence compared with NNRTI regimens, which allow higher levels of resistance, even with adherence above 95%. However, in failing PI/r regimens good adherence may prevent accumulation of further resistance mutations and therefore help to preserve future drug options. In contrast, adherence levels have little impact on NNRTI treatments once the first mutations have emerged.
Published: 2013
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49. Genetic Diversity of EBV-Encoded LMP1 in the Swiss HIV Cohort Study and Implication for NF-Κb Activation

Author: Zuercher, Emilie, Butticaz, Christophe, Wyniger, Josiane, Martinez, Raquel, Battegay, Manuel, Boffi El Amari, Emmanuelle, Dang, Thanh, Egger, Jean-François, Fehr, Jan, Mueller-Garamvögyi, Esther, Parini, Andrea, Schaefer, Stephan C, Schoeni-Affolter, Franziska, Thurnheer, Christine, Tinguely, Marianne, Telenti, Amalio, Rothenberger, Sylvia, Swiss HIV Cohort Study, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Rothenberger, Sylvia
Subjects: Herpesvirus 4, Human, DNA Mutational Analysis, lcsh:Medicine, HIV Infections, Polymerase Chain Reaction, Hematologic Cancers and Related Disorders, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, hemic and lymphatic diseases, Lymphocytes, lcsh:Science, Phylogeny, Genetics, 0303 health sciences, Multidisciplinary, Cancer Risk Factors, NF-kappa B, Transfection, Phenotype, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Medicine, Lymphomas, Research Article, Cell Survival, 610 Medicine & health, 1100 General Agricultural and Biological Sciences, Biology, Models, Biological, Microbiology, Virus, Viral Matrix Proteins, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, Virology, 10049 Institute of Pathology and Molecular Pathology, otorhinolaryngologic diseases, medicine, Humans, Transcription factor, 030304 developmental biology, 1000 Multidisciplinary, Polymorphism, Genetic, Activator (genetics), lcsh:R, HEK 293 cells, Genetic Variation, Cancers and Neoplasms, Cell Transformation, Viral, medicine.disease, Lymphoma, stomatognathic diseases, Nasopharyngeal carcinoma, Mutation, lcsh:Q, Cell Transformation, Viral/genetics, HIV Infections/virology, Herpesvirus 4, Human/genetics, Lymphocytes/virology, NF-kappa B/metabolism, Viral Matrix Proteins/metabolism
Abstract: Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1.
Published: 2012
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50. Tuberculosis in HIV-Negative and HIV-Infected Patients in a Low-Incidence Country: Clinical Characteristics and Treatment Outcomes

Author: Thomas Bodmer, Jacques Schrenzel, Sebastien Gagneux, Jean-Paul Janssens, Matthias Hoffmann, Enos Bernasconi, Erik C. Böttger, Lukas Fenner, Matthias Cavassini, Jan Fehr, Peter Helbling, Matthias Egger, Swiss HIV Cohort, Molecular Epidemiology of Tuberculosis Study Groups, Fenner, L., Egger, M., Gagneux, S., Tanner, M., Furrer, H., Böttger, EC., Frei, R., Bodmer, T., Ninet, B., Schrenzel, J., Jaton, K., Telenti, A., Siegrist, H., Pfyffer, GE., Bruderer, T., Dolina, M., Dubuis, O., Battegay, M., Bernasconi, E., Hoffmann, M., Cavassini, M., Hirschel, B., Calmy, A., Fehr, J., Janssens, JP., Stalder, JM., Helbling, P., Altpeter, E., Rieder, HL., Barth, J., Böni, J., Bucher, HC., Burton-Jeangros, C., Cellerai, C., Elzi, L., Fellay, J., Flepp, M., Francioli, P., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Fenner, Lukas
Subjects: Bacterial Diseases, CD4-Positive T-Lymphocytes, Male, Pediatrics, Viral Diseases, Epidemiology, lcsh:Medicine, HIV Infections, Comorbidity, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, Adult, CD4-Positive T-Lymphocytes/cytology, Female, HIV Infections/complications, HIV Infections/epidemiology, HIV Seropositivity, Humans, Incidence, Middle Aged, Prospective Studies, Risk, Switzerland, Transients and Migrants, Treatment Outcome, Tuberculosis/complications, Tuberculosis/epidemiology, 030212 general & internal medicine, Prospective cohort study, lcsh:Science, ddc:616, 0303 health sciences, Multidisciplinary, 10179 Institute of Medical Microbiology, Incidence (epidemiology), 1. No poverty, virus diseases, 3. Good health, Infectious Diseases, Cohort, Medicine, Developed country, Cohort study, Research Article, medicine.medical_specialty, Tuberculosis, 610 Medicine & health, 1100 General Agricultural and Biological Sciences, Microbiology, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, Virology, medicine, Biology, HIV Infections/complications/epidemiology/virology, 1000 Multidisciplinary, 030306 microbiology, business.industry, lcsh:R, Extensively drug-resistant tuberculosis, Tropical Diseases (Non-Neglected), HIV, medicine.disease, Tuberculosis/complications/epidemiology/virology, 570 Life sciences, biology, lcsh:Q, business
Abstract: BACKGROUND: In Switzerland and other developed countries, the number of tuberculosis (TB) cases has been decreasing for decades, but HIV-infected patients and migrants remain risk groups. The aim of this study was to compare characteristics of TB in HIV-negative and HIV-infected patients diagnosed in Switzerland, and between coinfected patients enrolled and not enrolled in the national Swiss HIV Cohort Study (SHCS). METHODS AND FINDINGS: All patients diagnosed with culture-confirmed TB in the SHCS and a random sample of culture-confirmed cases reported to the national TB registry 2000-2008 were included. Outcomes were assessed in HIV-infected patients and considered successful in case of cure or treatment completion. Ninety-three SHCS patients and 288 patients selected randomly from 4221 registered patients were analyzed. The registry sample included 10 (3.5%) coinfected patients not enrolled in the SHCS: the estimated number of HIV-infected patients not enrolled in the SHCS but reported to the registry 2000-2008 was 146 (95% CI 122-173). Coinfected patients were more likely to be from sub-Saharan Africa (51.5% versus 15.8%, P
Published: 2012
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