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1. 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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2. Clostridium difficile infection is associated with graft loss in solid organ transplant recipients

Author: Cusini, A, Béguelin, C, Stampf, S, Boggian, K, Garzoni, C, Koller, M, Manuel, O, Meylan, P, Mueller, NJ, Hirsch, HH, Weisser, M, Berger, C, van Delden, C, Achermann, R, Amico, P, Aubert, JD, Banz, V, Beldi, G, Benden, C, Binet, I, Bochud, PY, Bucher, H, Bühler, L, Carell, T, Catana, E, Chalandon, Y, de Geest, S, de Rougemont, O, Dickenmann, M, Duchosal, M, Elkrief, L, Fehr, T, Ferrari-Lacraz, S, Gasche Soccal, P, Gaudet, C, Giostra, E, Golshayan, D, Hadaya, K, Halter, J, Heim, D, Hess, C, Hillinger, S, Hofbauer, G, Huynh-Do, U, Immer, F, Klaghofer, R, Laesser, B, Lehmann, R, Lovis, C, Marti, HP, Martin, PY, Mohacsi, P, Morel, P, Mueller, U, Mueller-McKenna, H, Müller, A, Müller, T, Müllhaupt, B, Nadal, D, Pascual, M, Passweg, J, Rick, J, Roosnek, E, Rosselet, A, Rothlin, S, Ruschitzka, F, Schanz, U, Schaub, S, Schnyder, A, Seiler, C, Steiger, J, Stirnimann, G, Toso, C, Venetz, JP, Villard, J, Wick, M, Wilhelm, M, Yerly, P, Gasche-Soccal, Paola Marina Alessandra, University of Zurich, and van Delden, C
Subjects: Graft Rejection, Male, genetic structures, 2747 Transplantation, 10265 Clinic for Endocrinology and Diabetology, 030230 surgery, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Postoperative Complications, Risk Factors, Medicine, 2736 Pharmacology (medical), Immunology and Allergy, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, 610 Medicine & health, Prospective cohort study, ddc:616, Incidence, Hazard ratio, Graft Survival, Clostridium difficile, Middle Aged, Prognosis, Anti-Bacterial Agents, Diarrhea, 10209 Clinic for Cardiology, 2723 Immunology and Allergy, Female, medicine.symptom, 10178 Clinic for Pneumology, Switzerland, Cohort study, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, Humans, Transplantation, business.industry, Clostridioides difficile, Case-control study, Organ Transplantation, Confidence interval, Transplant Recipients, 10036 Medical Clinic, Case-Control Studies, Clostridium Infections, business, Follow-Up Studies
Abstract: © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P =.02). These findings may help to improve the management of SOT recipients. ispartof: American Journal of Transplantation vol:18 issue:7 pages:1745-1754 ispartof: location:United States status: published
Published: 2017

3. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study

Author: Steering, D, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Ryom, L, Hatleberg, Ci, Sabin, Ca, Kamara, D, Smith, C, Phillips, A, Mocroft, A, Bojesen, A, Grevsen, A, Matthews, C, Raben, D, Lundgren, Jd, Brandt, Rs, Rickenbach, M, Fanti, I, Hillebreght, M, Zaheri, S, Gras, L, Pernot, E, Mourabi, J, Sundström, A, Delforge, M, Fontas, E, Torres, F, Mcmanus, H, Wright, S, Kristensen, D, Sjøl, A, Meidahl, P, Helweg-Larsen, J, Schmidt Iversen, J, Kirk, O, Reiss, P, Smit, C, Ross, M, Fux, Ca, Morlat, P, Moranne, O, Kamara, Da, Weber, R, Pradier, C, Friis-Møller, N, Kowalska, J, Sabin, C, Law, M, d'Arminio Monforte, A, Dabis, F, Bruyand, M, Bonnet, F, Bower, M, Fätkenheuer, G, Donald, A, Grulich, A, Prins, Jm, Kuijpers, Tw, Scherpbier, Hj, van der Meer JT, Wit, Fw, Godfried, Mh, van der Poll, T, Nellen, Fj, 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 AM, Mutschelknauss, M, Nobel, He, Pijnappel, Fj, Westerman, Am, Jurriaans, S, Back, Nk, Zaaijer, Hl, Berkhout, B, Cornelissen, Mt, Schinkel, Cj, Thomas, Xv, De Ruyter Ziekenhuis, A, van den Berge, M, Stegeman, A, Baas, S, de Looff, L, Versteeg, D, Pronk, Mj, Ammerlaan, Hs, Korsten-Vorstermans, Em, de Munnik ES, Jansz, Ar, Tjhie, J, Wegdam, Mc, Deiman, B, Scharnhorst, V, Kinderziekenhuis, E, van der Plas, A, Weijsenfeld, Am, van der Ende ME, de Vries-Sluijs TE, van Gorp EC, Schurink, Ca, Nouwen, Jl, Verbon, A, Rijnders, Bj, Bax, Hi, Hassing, Rj, van der Feltz, M, Bassant, N, van Beek JE, Vriesde, M, van Zonneveld LM, de Oude-Lubbers, A, van den Berg-Cameron HJ, Bruinsma-Broekman, Fb, de Groot, J, de Man de, Z, Broekhoven-Kruijne, Mj, Schutten, M, Osterhaus, Ad, Boucher, Ca, Driessen, Gj, van Rossum AM, van der Knaap LC, Visser, E, Branger, J, Duijf-van de Ven CJ, Haag, D, Schippers, Ef, van Nieuwkoop, C, Brimicombe, Rw, van IJperen, M, van der Hut, G, Franck, Pf, van Eeden, A, Brokking, W, Groot, M, Damen, M, Kwa, Is, Groeneveld, Ph, Bouwhuis, Jw, van den Berg JF, van Hulzen AG, van der Bliek GL, Bor, Pc, Bloembergen, P, Wolfhagen, Mj, Ruijs, Gj, Gasthuis, K, van Lelyveld SF, Soetekouw, R, Hulshoff, N, van der Prijt LM, Schoemaker, M, Bermon, N, van der Reijden WA, Jansen, R, Herpers, Bl, Veenendaal, D, Kroon, Fp, Arend, Sm, de Boer MG, Bauer, Mp, Jolink, H, Vollaard, Am, Dorama, W, Moons, C, Claas, Ec, Kroes, Ac, den Hollander JG, Pogany, K, Kastelijns, M, Smit, Jv, Smit, E, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, Sh, Oude Lashof, A, Posthouwer, D, Ackens, Rp, Schippers, J, Vergoossen, R, Weijenberg Maes, B, Savelkoul, Ph, Loo, Ih, Zuiderzee, Mc, Weijer, S, El Moussaoui, R, Heitmuller, M, Kortmann, W, van Twillert, G, Cohen Stuart JW, Diederen, Bm, Pronk, D, van Truijen-Oud FA, van der Reijden, W, Leyten, Em, Gelinck, Lb, van Hartingsveld, A, Meerkerk, C, Wildenbeest, Gs, Mutsaers, Ja, Jansen, Cl, van Vonderen MG, van Houte DP, Dijkstra, K, Faber, S, Weel, J, Kootstra, Gj, Delsing, Ce, van der Burgvan de Plas, M, Heins, H, Lucas, E, Brinkman, K, Frissen, Ph, Blok, Wl, Schouten, We, Bosma, As, Brouwer, Cj, Geerders, Gf, Hoeksema, K, Kleene, Mj, van der Meché IB, Toonen, Aj, Wijnands, S, van Ogtrop ML, Koopmans, Pp, Keuter, M, van der Ven AJ, ter Hofstede HJ, Dofferhoff, As, van Crevel, R, Albers, M, Bosch, Me, Grintjes-Huisman, Kj, Zomer, Bj, Stelma, Ff, Burger, D, Richter, C, van der Berg JP, Gisolf, Eh, Beest, G, van Bentum PH, Langebeek, N, Tiemessen, R, Swanink, Cm, Veenstra, J, Lettinga, Kd, Spelbrink, M, Sulman, H, Witte, E, Peerbooms, Pg, Mulder, Jw, Vrouenraets, Sm, Lauw, Fn, van Broekhuizen MC, Paap, H, Vlasblom, Dj, Oudmaijer Sanders, E, Smits, Ph, Rosingh, Aw, Verhagen, Dw, Geilings, J, van Kasteren ME, Brouwer, Ae, de Kruijf-van de Wiel BA, Kuipers, M, Santegoets, Rm, van der Ven, B, Marcelis, Jh, Buiting, Ag, Kabel, Pj, Bierman, Wf, Sprenger, Hg, Scholvinck, Eh, van Assen, S, Wilting, Kr, Stienstra, Y, de Groot-de Jonge, H, van der Meulen PA, de Weerd DA, Niesters, Hg, Riezebos-Brilman, A, van Leer-Buter CC, Hoepelman, Ai, Schneider, Mm, Mudrikova, T, Ellerbroek, Pm, Oosterheert, Jj, Arends, Je, Barth, Re, Wassenberg, Mw, van Elst-Laurijssen DH, Laan, Lm, van Oers-Hazelzet EE, Patist, J, Vervoort, S, Nieuwenhuis, He, Frauenfelder, R, Schuurman, R, Verduyn-Lunel, F, Wensing, Am, Peters, Ej, van Agtmael MA, Perenboom, Rm, Bomers, M, de Vocht, J, Elsenburg, Lj, Pettersson, Am, Vandenbroucke-Grauls, Cm, Ang, Cw, Geelen, Sp, Wolfs, Tf, Bont, Lj, Nauta, N, Bezemer, Do, van Sighem AI, Hillebregt, M, Kimmel, V, Tong, Y, Lascaris, B, van den Boogaard, R, Hoekstra, P, de Lang, A, Berkhout, M, Grivell, S, Jansen, A, de Groot, L, van den Akker, M, Bergsma, D, Lodewijk, C, Meijering, R, Peeck, B, Raethke, M, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Tuijn, E, Veenenberg, L, Woudstra, T, Bakker, Y, de Jong, A, Broekhoven, M, Claessen, E, Rademaker, Mj, Munjishvili, L, Kruijne, E, Tuk, B, Bouchet, S, Breilh, D, Chêne, G, Dupon, M, Fleury, H, Gaborieau, V, Lacoste, D, Malvy, D, Mercié, P, Neau, D, Pellegrin, I, Pellegrin, Jl, Tchamgoué, S, Fagard, C, Lawson-Ayayi, S, Richert, L, Thiébaut, R, Wittkop, L, André, K, Bernard, N, Caunègre, L, Cazanave, C, Ceccaldi, J, Chossat, I, Courtault, C, Dauchy, Fa, De Witte, S, Dondia, D, Dupont, A, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Gerard, Y, Greib, C, Hessamfar-Joseph, M, Imbert, Y, Lataste, P, Lazaro, E, Marie, J, Mechain, M, Meraud, Jp, Monlun, E, Ochoa, A, Pillot-Debelleix, M, Pistone, T, Raymond, I, Receveur, Mc, Rispal, P, Sorin, L, Valette, C, Vandenhende, Ma, Vareil, Mo, Viallard, Jf, Wille, H, Wirth, G, Moreau, Jf, Lafon, Me, Reigadas, S, Trimoulet, P, Haramburu, F, Miremont-Salamé, G, Blaizeau, Mj, Crespel, I, Decoin, M, Delveaux, S, Diarra, F, D'Ivernois, C, Hanappier, C, Leleux, O, Le Marec, F, Lenaud, E, Mourali, J, Pougetoux, A, Uwamaliya-Nziyumvira, B, Tsaranazy, A, Valdes, A, Conte, V, Louis, I, Palmer, G, Sapparrart, V, Touchard, D, Petoumenos, K, Bendall, C, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Nicholson, J, Bloch, M, Franic, T, Baker, D, Vale, R, Carr, A, Cooper, D, Chuah, J, Ngieng, M, Nolan, D, Skett, J, Calvo, G, Mateu, S, Domingo, P, Sambeat, Ma, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, De Wit, S, Clumeck, N, Necsoi, C, Gennotte, Af, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, Mc, Semaille, P, Van, Y, Neaton, J, Bartsch, G, El-Sadr, Wm, Krum, E, Thompson, G, Wentworth, D, 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, Losso, M, Kundro, M, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, Vm, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Hansen, Ab, Pedersen, C, Møller, Nf, Ostergaard, L, Dragsted, Ub, Nielsen, Ln, Zilmer, K, Smidt, J, Ristola, M, Aho, I, Katlama, C, Viard, Jp, Girard, Pm, Cotte, L, Duvivier, C, Rockstroh, J, Schmidt, R, van Lunzen, J, Degen, O, Stellbrink, Hj, Stefan, C, Bogner, J, Chkhartishvili, N, Kosmidis, J, Gargalianos, P, Xylomenos, G, Lourida, P, Sambatakou, H, Banhegyi, D, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Sthoeger, Zm, D'Arminio Monforte, A, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, D'Offizi, G, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Matulionyte, R, Staub, T, Hemmer, R, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Horban, A, Bakowska, E, Grzeszczuk, A, Flisiak, R, Parczewski, M, Pynka, M, Maciejewska, K, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Doroana, M, Caldeira, L, Mansinho, K, Maltez, F, Radoi, R, Oprea, C, Rakhmanova, A, Trofimora, T, Khromova, I, Kuzovatova, E, Jevtovic, D, Shunnar, A, Staneková, D, Tomazic, J, Moreno, S, Rodriguez, J, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gatell, Jm, Miró, Jm, Gutierrez, M, Mateo, G, Laporte, Jm, Blaxhult, A, Flamholc, L, Falconer, K, Thalme, A, Sonnerborg, A, Ledergerber, B, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Elzi, L, Schmid, P, Kravchenko, E, Chentsova, N, Frolov, V, Kutsyna, G, Baskakov, I, Servitskiy, S, Kuznetsova, A, Kyselyova, G, Gazzard, B, Johnson, Am, Simons, E, Johnson, Ma, Orkin, C, Weber, J, Scullard, G, Fisher, M, Leen, C, Lundgren, J, Grarup, J, Cozzi-Lepri, A, Thiebaut, R, Peters, L, Fischer, Ah, Grønborg Laut, K, Larsen, Jf, Podlekareva, D, Grint, D, Shepherd, L, Schultze, A, Morfeldt, L, Thulin, G, Åkerlund, B, Koppel, K, Karlsson, A, Håkangård, C, Moroni, M, Angarano, G, Armignacco, O, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Perno, Cf, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bonfanti, P, Bonora, S, Borderi, M, Capobianchi, R, 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, Quiros Roldan, E, Rusconi, S, Cicconi, P, Formenti, T, Galli, L, Lorenzini, P, Giacometti, A, Costantini, A, Santoro, C, Suardi, C, Vanino, E, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, Pe, Piano, P, Vecchiet, J, Falasca, K, Sighinolfi, L, Segala, D, Cassola, G, Viscoli, G, Alessandrini, A, Piscopo, R, Mazzarello, G, Mastroianni, C, Belvisi, V, Castelli, A, Rizzardini, G, Ridolfo, Al, Piolini, R, Salpietro, S, Carenzi, L, Moioli, Mc, Puzzolante, C, Abrescia, N, Chirianni, A, Guida, Mg, Onofrio, M, Baldelli, F, Francisci, D, Parruti, G, Ursini, T, Magnani, G, Ursitti, Ma, D'Avino, A, Gallo, L, Nicastri, E, Capozzi, M, Libertone, R, Tebano, G, Cattelan, A, Mura, Ms, Caramello, P, Orofino, Gc, Sciandra, M, Pellizzer, G, Manfrin, V, Castelli, Ap, Dollet, K, Caissotti, C, Dellamonica, P, Bernard, E, Cua, E, De Salvador-Guillouet, F, Durant, J, Ferrando, S, Dunais, B, Mondain-Miton, V, Naqvi, A, Perbost, I, Prouvost-Keller, B, Pillet, S, Pugliese, P, Risso, K, Roger, Pm, Aubert, V, Bernasconi, E, Böni, J, Bucher, Hc, Burton-Jeangros, C, Dollenmaier, G, Egger, M, Fehr, J, Fellay, J, 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, Martinetti, G, Martinez de Tejada, B, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni-Affolter, F, Schüpbach, J, Speck, R, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Yerly, S., University College of London [London] (UCL), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Chemical Biology, Internal Medicine, Medical Microbiology & Infectious Diseases, Pediatrics, Virology, Mocroft, A:, Lundgren, Jd, Ross, M, Fux, Ca, Reiss, P, Moranne, O, Morlat., P, Monforte, Ad, Kirk, O, Ryom, L, for the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D), Study, Lazzarin, A, Castagna, A, Other departments, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Center of Experimental and Molecular Medicine, Graduate School, Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, APH - Health Behaviors & Chronic Diseases, Med Microbiol, Infect Dis & Infect Prev, MUMC+: DA MMI Staf (9), MUMC+: MA Alg Interne Geneeskunde (9), MUMC+: DA MMI Infectieserologie (9), MUMC+: DA MMI AIOS (9), RS: FHML non-thematic output, Mocroft, A, Lundgren, J, Fux, C, Morlat, P, Monforte, A, and Gori, A
Subjects: 0301 basic medicine, Male, PROTEASE INHIBITOR, Epidemiology, Infectious Diseases, Immunology, Virology, Research Support, U.S. Gov't, P.H.S, HIV Infections, SDG 3 – Goede gezondheid en welzijn, Rate ratio, THERAPY, chemistry.chemical_compound, 0302 clinical medicine, HIV, antiretroviral, kidney disease, immune system diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, HIV Infection, 030212 general & internal medicine, Prospective Studies, Renal Insufficiency, Chronic, Prospective cohort study, Research Support, Non-U.S. Gov't, Antiretrovirals, virus diseases, Lopinavir, ASSOCIATION, Middle Aged, 3. Good health, Europe, Antiretrovirals, HIV, chronic kidney disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, NAIVE PATIENTS, CREATININE, Human, Cohort study, medicine.drug, Glomerular Filtration Rate, United State, Adult, medicine.medical_specialty, TENOFOVIR DISOPROXIL FUMARATE, RENAL-FUNCTION, Adolescent, Anti-HIV Agents, Atazanavir Sulfate, Renal function, Infectious Disease, Australia, Humans, Renal Insufficiency, Chronic, Tenofovir, United States, Young Adult, NO, 03 medical and health sciences, EFAVIRENZ, SDG 3 - Good Health and Well-being, Internal medicine, Journal Article, medicine, Creatinine, business.industry, Anti-HIV Agent, medicine.disease, 030112 virology, Atazanavir, INFECTED INDIVIDUALS, Prospective Studie, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, RISK-FACTORS, business, chronic kidney disease, Kidney disease
Abstract: BACKGROUND: Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR).METHODS: In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir.FINDINGS: Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], pINTERPRETATION: In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored.FUNDING: The Highly Active Antiretroviral Therapy Oversight Committee.
Published: 2016
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4. Tuberculosis-related mortality in people living with HIV in Europe and Latin America: An international cohort study

Author: Podlekareva Daria, N, Efsen Anne Marie, W, Schultze, A, Post Frank, A, Skrahina Alena, M, Panteleev, A, Furrer, H, Miller Robert, F, Losso, M. H, Toibaro, J, Miro Jose, M, Vassilenko, A, Girardi, Enrico, Bruyand, M, Obel, N, Lundgren Jens, D, Mocroft, A, Kirk, O, Karpov, I, Skrahina, A, Klimuk, D, Skrahin, A, Kondratenko, O, Zalutskaya, A, Bondarenko, V, Mitsura, V, Kozorez, E, Tumash, O, Suetnov, O, Paduto, D, Iljina, V, Kummik, T, Bolokadze, N, Mshvidobadze, K, Lanchava, N, Goginashvili, L, Mikiashvili, L, Bablishvili, N, Rozentale, B, Zeltina, I, Janushkevich, I, Caplinskiene, I, Caplinskas, S, Kancauskiene, Z, Podlasin, R, Wiercinska Drapalo, A, Thompson, M, Kozlowska, J, Grezesczuk, A, Bura, M, Knysz, B, Inglot, M, Garlicki, A, Loster, J, Duiculescu, D, Tetradov, S, Rakhmanova, A, Panteleeva, O, Yakovlev, A, Kozlov, A, Tyukalova, A, Vlasova, Y, Trofimov, T, Kyselyova, G, Thorsteinsson, K, Payen, Mc, Kabeya, K, Necsoi, C, Dabis, F, Morlat, P, Dupont, A, Gerard, Y, Bonnal, F, Ceccaldi, J, De Witte, S, Monlun, E, Lataste, P, Chossat, I, Sagette, M, Rickenbach, M, Elzi, L, Battegay, M, Sculier, D, Calmy, A, Cavassini, M, Bruno, A, Bernasconi, E, Hoffmann, M, Vernazza, P, Fehr, J, Weber, R, Aubert, V, Böni, J, Bucher, Hc, Burton Jeangros, C, Dollenmaier, G, Egger, M, Fellay, J, 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, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni Affolter, F, Schmid, P, Schüpbach, J, Speck, R, Tarr, P, Telenti, A, Trkola, A, Yerly, S, Miller, Rf, Vora, N, Cooke, G, Mullaney, S, Wilkins, E, George, V, Collini, P, Dockrell, D, Post, F, Campbell, L, Brum, R, Mabonga, E, Saigal, P, Kegg, S, Ainsworth, J, Waters, A, Dhar, J, Mashonganyika, L, Girardi, E, Rianda, A, Galati, V, Pinnetti, C, Tommasi, C, Lapadula, G, Di Biagio, A, Parisini, A, Carbonara, S, Angarano, G, Purgatorio, M, Matteelli, Alberto, Apostoli, A, Miro, Jm, Manzardo, C, Ligero, C, Gonzalez, J, Martinez Martinez, Ja, Sanchez, F, Knobel, H, Salvadó, M, Lopez Colomes, Jl, Martínez Lacasa, X, Cuchí, E, Falcó, V, Curran, A, Tortola, Mt, Ocaña, I, Vidal, R, Sambeat, Ma, Pomar, V, Coll, P, Pozamczer, D, Saumoy, M, Alcaide, F, Caylà, J, Moreno, A, Millet, Jp, Orcau, A, Fina, L, Romero, A, Roldan, Ll, Iribarren, Ja, Ibarguren, M, Moreno, S, González, A, Miralles, P, Aldámiz Echevarría, T, Losso, M, Gambardella, L, Macias, L, Warley, E, Tavella, S, Messina, O, Gear, O, Laplume, H, Marson, C, Contarelia, J, Michaan, M, Scapellato, P, Alessandro, D, Bartoletti, B, Palmero, D, Elias, C, Cortes, C, Crabtree, B, Gomez, Jl, Hernandez, La, and Badial, F.
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Latin Americans, Tuberculosis, Anti-HIV Agents, Epidemiology, 030106 microbiology, Population, Infectious Diseases, Immunology, Virology, Antitubercular Agents, HIV Infections, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Tuberculosis, Multidrug-Resistant, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Young adult, Epidemics, education, Prospective cohort study, education.field_of_study, AIDS-Related Opportunistic Infections, business.industry, Mortality rate, Middle Aged, medicine.disease, Europe, Latin America, Female, business, Developed country, Demography, Cohort study
Abstract: Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study.Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models.Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p0·0001).Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe.EU Seventh Framework Programme.
Published: 2016

5. Diagnostik der Lyme-Borreliose

Author: Steffen I and Hirsch Hh
Subjects: Gynecology, medicine.medical_specialty, business.industry, Lyme borreliosis, medicine, Diagnostic test, General Medicine, business
Abstract: Die Verschiedenartigkeit der in Europa vorkommenden Borrelien, zusammengefasst als Borrelia burgdorferi sensu lato, erlaubt nicht, die für Borrelia burgdorferi sensu stricto in USA etablierten Definitionen und Tests ohne weiteres zu übernehmen. Durch die Erweiterung um Antigene der in Europa zusätzlich vorkommenden Subspezies B. afzelii und B. garinii bleibt der Nachweis der Borrelien-spezifischen Antikörper weiterhin der wichtigste Test in der Borrelien-Diagnostik: Screening mittels ELISA, Bestätigung durch Immunoblot. Der Erregernachweis mittels PCR oder, in spezialisierten Labors auch mittels Kultur, spielt trotz der hohen Spezifität wegen der tiefen Sensitivität nur eine untergeordnete Rolle. Unverändert gilt, dass Expositionsrisiko, Stadium und klinischer Verlauf die Wahl und Interpretation der diagnostischen Tests bestimmen.
Published: 2005
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6. Virale Infektionen nach Transplantation

Author: Hirsch Hh
Subjects: Gynecology, medicine.medical_specialty, business.industry, medicine, General Medicine, business
Abstract: Morbidität und Mortalität einer Virusinfektion wird maßgeblich bestimmt durch Determinanten des Patienten (z. B. die Qualität und Quantität der Immuneffektoren, Grunderkrankung, Alter), des Grafts (z. B. Organ, HLA-mismatching, Schädigung, Permissivität für Virusinfektion) und des Virus (z. B. Genus, Tropismus, Fitness, Virostatikaresistenz). Diese «ménage-à-trois» von Patient, Graft und Virus wird durch zum Teil dosisabhängige Faktoren moduliert wie Immunsuppression, lokales und systemisches Entzündungs- und Zytokinmuster, Gabe von Immunglobulinen und/oder Virostatika. Diese Konzepte sind bei Infektionen mit Zytomegalievirus (CMV) am besten untersucht. Drei Gründe sind dafür verantwortlich: 1. Klinisch-virologische Definitionen von Infektion und Erkrankung; 2. quantitative Testverfahren mit schneller Ergebniserstellung; 3. Verfügbarkeit wirksamer Virostatika. Aus der spezifischen Transplantationskonstellation ergibt sich der prophylaktische, präemptive oder therapeutische Einsatz von Virostatika und Immunglobulinen. Weitere Fortschritte könnten sich durch die bessere Charakterisierung der zellulären Immunität ergeben. Mit der breiten Verfügbarkeit von quantitativen molekularen Messverfahren sind nun ebenfalls Fortschritte bei anderen, transplantationsrelevanten Virusinfektionen zu erwarten wie zum Beispiel Epstein-Barr-Virus, Polyomavirus BK oder respiratorische Viren.
Published: 2003
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7. Adhärenz, pharmakokinetischer «Toleranzbereich» und HIV-Resistenzbildung

Author: Erik Mossdorf and Hirsch Hh
Subjects: Gynecology, medicine.medical_specialty, business.industry, Medicine, General Medicine, business
Abstract: Anlässlich einer Kontrolle wird bei einem 43-jährigen, HIV-positiven Patienten mit ART neu eine HIV-Viruslast von 2032 Kopien/mL festgestellt. Zuvor war unter einer Therapie mit Lamivudin und Zidovudin (NRTI) sowie Nelfinavir (nicht-geboosteter PI) die Viruslast während 18 Monaten undetektierbar (< 50 Kopien/mL). Es konnte die Diagnose einer sekundären HIV-Resistenz des ungeboosteten PIs bei pharmakokinetischer Non-Adhärenz gestellt werden. Die HIV-Resistenzprüfung legte eine Salvage-Therapie mit einem geboosteten PI nahe. Neben der regelmässigen Medikamenteneinnahme erbringen diese antiretroviralen Medikamente mit ihren hohen Serumspiegeln und langen Halbwertszeiten eine dauerhafte Virussuppression und vermindern das Risiko von Resistenzentwicklungen.
Published: 2006
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8. 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

9. Koagulase-negative Staphylokokken auf der Haut – immer harmlos?

Author: Ramseier E, Fehr J, and Hirsch Hh
Subjects: biology, business.industry, Medicine, General Medicine, Staphylococcus lugdunensis, biology.organism_classification, business, Microbiology
Abstract: Beschrieben werden rezidivierende Hautinfektionen (Furunkulose, Follikulitis) mit koagulase-negativen Staphylokokken. Die Speziesbestimmung ergab Staph. lugdunensis, der Staph. aureus-ähnlich Virulenz zeigen kann. Eine Dekontaminationsstrategie war nachhaltig erfolgreich. Gegebenfalls ist eine Behandlung von kolonisierten/symptomatischen Familienmitgliedern indiziert.
Published: 2004
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10. Wie häufig kann die klinische Diagnose des Dreitagefiebers mit der HHV-6-Serologie bestätigt werden?

Author: Hirsch Hh and Rudin C
Subjects: medicine.medical_specialty, biology, business.industry, Roseola Infantum, medicine.disease_cause, biology.organism_classification, Dermatology, Herpesviridae, Serology, Private practice, Alphaherpesvirinae, Pediatrics, Perinatology and Child Health, Immunology, medicine, biology.protein, Viral disease, Seroconversion, Antibody, business
Abstract: Three years ago a newly recognized human herpes virus (HHV-6) was identified to be the causative agent for exanthem subitum (roseola infantum). So far this diagnosis was suggested chiefly by excluding other infections and the presence of a typical course of the disease. To find out how often the clinical diagnosis can be confirmed serologically, we asked five pediatricians in private practice as well as residents of the out-patient and infant departments of our hospital to obtain paired heparinized blood samples of any child suspicious for exanthem subitum. 36 children with clinically suspected exanthem subitum and a mean age of 14.2 (5-71) months were included in this prospective study. Indirect immunofluorescence was used to detect IgG and IgM antibodies to HHV-6. In 22 children (61%) the clinical diagnosis was confirmed serologically. IgM antibody was found in only 16 of these 22 children. In 8 patients the results were ambiguous. Three had in the same time a doubtful seroconversion to other viruses of the herpes group (HSV twice; EBV once), in four children there was an insufficient rise in IgG antibodies without presence of an IgM response, and once we found a very high HHV-6 specific antibody titre (greater than 1:80) in both serum samples. In 6 children neither a seroconversion nor a rise in HHV-6 antibody titre were found. Retrospectively, only three of these children had a clinical course really typical for exanthem subitum. We conclude that in most cases the clinical diagnosis of exanthem subitum will be confirmed by serological examination.(ABSTRACT TRUNCATED AT 250 WORDS)
Published: 1991
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11. Current preventive strategies and management of Epstein–Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey

Author: San Juan, R, Manuel, O, Hirsch, Hh, Fernández Ruiz, M, López Medrano, F, Comoli, P, Caillard, S, Grossi, P, Aguado, Jm, Álamo Martínez JM, Anaya, F, Anttila, Vj, Arnol, M, Avolio, Aw, Baccarani, U, Castello, Ib, Boletis, I, Bonofiglio, R, Viamigliori, A, Bressollette, C, Brockmann, J, Pulido, Jc, Catalán, P, Christiansen, C, Cofan, F, Cordero, E, Leiro, Mc, Dantal, J, D'Armini, A, Delgado, Jf, Dello Strologo, L, Gesu, B, DI RAIMONDO, Francesco, Dierickx, D, Eis Hübinger, A, Kremer, Sf, Faggian, G, Fariñas, Mc, Folgueira, Md, Fontana, I, Franco, A, Furian, L, Garzoni, C, Ghirardo, G, Ginevri, F, Grinyó, J, Grossi, Pa, Gupte, G, Hansson, L, Helanterä, I, Herrero, Ji, Hobin, D, Hoffmann, D, Jan, L, Jarque, I, Jespersen, B, Kaczmarek, I, Klin, G, Kevin, P, Koneth, I, Kovac, D, Lacaille, F, Lautenschlager, I, Len, O, Lladó, L, Loy, M, Maeso, Ma, Marianne, Lv, Marsh, J, Meylan, P, Miñambres, E, Montejo, M, Mueller, N, Muñoz, P, Nadalin, S, Kamar, N, Nicolas, B, Olivier, D, Palomo, J, Pascual, M, Peter, J, Pierre, F, Portero, Mf, Provot, F, Boluda, Er, Regalia, E, Reina, G, Reuter, S, Ricart, Mj, García, Mr, Rollag, H, Russo, Fp, Sabé, N, Salcedo, M, Santambrogio, L, Seeman, T, Serra, N, Sgarabotto, D, Simonek, J, Thierry, Y, Thomsen, Mk, Tihic, N, Torre Cisneros, J, Travi, G, Tulissi, P, Moal, V, Veroux, Massimiliano, Santandreu, Av, Vizzini, G, Zibar, L., Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Department of Virology, and Medicum
Subjects: Epstein-Barr Virus Infections, Cross-sectional study, Settore MED/18 - CHIRURGIA GENERALE, medicine.medical_treatment, Medizin, Epstein-Barr virus, Europe, Post-transplant lymphoproliferative disease, Pre-emptive treatment, Survey, Microbiology (medical), Infectious Diseases, medicine.disease_cause, Organ transplantation, Epstein–Barr virus, Surveys and Questionnaires, hemic and lymphatic diseases, Medicine, Tomography, TOR Serine-Threonine Kinases, Immunosuppression, General Medicine, Viral Load, pre-emptive treatment, X-Ray Computed, 3. Good health, Cross-Sectional Studies, Humans, Immunosuppressive Agents, Lymphoproliferative Disorders, Positron-Emission Tomography, Rituximab, Tomography, X-Ray Computed, Viremia, Organ Transplantation, Transplant Recipients, post-transplant lymphoproliferative disease, Viral load, medicine.drug, medicine.medical_specialty, survey, Internal medicine, business.industry, Immunology, 3111 Biomedicine, business, Solid organ transplantation, Serostatus
Abstract: There is limited clinical evidence on the utility of the monitoring of Epstein–Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients.
Published: 2015
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12. Die elektrophysiologischen Voraussetzungen des ventrikel-gesteuerten Herzschrittmachers

Author: Stauch M and Hirsch Hh
Subjects: Pulmonary and Respiratory Medicine, Gynecology, medicine.medical_specialty, business.industry, Medicine, Surgery, Cardiology and Cardiovascular Medicine, business
Published: 1967
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13. Störungen bei der Verwendung des ventrikelgesteuerten Herzschrittmachers

Author: Eisenbach J, Hirsch Hh, and Pocai Br
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Text mining, medicine.anatomical_structure, business.industry, Ventricle, Internal medicine, Cardiology, Medicine, Surgery, Cardiology and Cardiovascular Medicine, business
Published: 1968
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14. Komplikationen bei der Schrittmacherimplantation

Author: Eisenbach J, Hirsch Hh, and Scior H
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, business.industry, MEDLINE, Medicine, Surgery, Cardiology and Cardiovascular Medicine, business, Pacemaker implantation
Published: 1966
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15. Extra- oder intrathorakale Herzmassage beim akuten Kreislaufstillstand

Author: Hartel W, Hirsch Hh, and Ungeheuer E
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Heart block, business.industry, Carotid arteries, Femoral artery, medicine.disease, Internal medicine, medicine.artery, medicine, Cardiology, Surgery, Heart massage, Cardiology and Cardiovascular Medicine, business
Published: 1963
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16. Spülung durch den Blutstrom als Ursache der Beständigkeit des homologen Herzklappengewebes nach der Transplantation

Author: Hirsch Hh and Hanke H
Subjects: Pulmonary and Respiratory Medicine, Aortic valve, medicine.medical_specialty, business.industry, medicine.anatomical_structure, Internal medicine, medicine, Homologous chromosome, Cardiology, Flushing, Surgery, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Blood stream
Published: 1969
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17. 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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18. 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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19. 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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20. 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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21. 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

22. 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

23. 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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24. Reply to Cunha et al

Author: Wójtowicz, Agnieszka, Lecompte, Thanh Doco, Bibert, Stéphanie, Manuel, Oriol, Rüeger, Sina, Berger, Christoph, Boggian, Katia, Cusini, Alexia, Garzoni, Christian, Khanna, Nina, Mueller, Nicolas J, Meylan, Pascal R, Pascual, Manuel, Van Delden, Christian, Semmo, Nasser, Beldi, Guido, Bochud, Pierre-Yves, Swiss Transplant, Cohort Study, Swiss Transplant Cohort Study, Achermann, R., Aubert, JD., Baumann, P., Beldi, G., Benden, C., Berger, C., Binet, I., Bochud, PY., Boely, E., Bucher, H., Bühler, L., Carell, T., Catana, E., Chalandon, Y., de Geest, S., de Rougemont, O., Dickenmann, M., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Gasche, Y., Soccal, PG., Giostra, E., Golshayan, D., Good, D., Hadaya, K., Hess, C., Hillinger, S., Hirsch, HH., Hofbauer, G., Huynh-Do, U., Immer, F., Klaghofer, R., Koller, M., Kuntzen, T., Laesser, B., Lehmann, R., Lovis, C., Manuel, O., Marti, HP., Martin, PY., Meylan, P., Mohacsi, P., Morard, I., Morel, P., Mueller, U., Mueller, NJ., Mueller-McKenna, H., Müller, T., Müllhaupt, B., Nadal, D., Nair, G., Pascual, M., Passweg, J., Ziegler, CP., Rick, J., Roosnek, E., Rosselet, A., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Seiler, C., Semmo, N., Stampf, S., Steiger, J., Toso, C., Tsinalis, D., Van Delden, C., Venetz, JP., Villard, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, Bochud, Pierre-Yves, and Chalandon, Yves
Subjects: Male, Microbiology (medical), medicine.medical_specialty, Organ Transplantation / adverse effects, Serum Amyloid P-Component / genetics, 610 Medicine & health, 2726 Microbiology (medical), Organ transplantation, 10234 Clinic for Infectious Diseases, Immunocompromised Host, Internal medicine, medicine, Humans, Serum amyloid P component, ddc:616, Mycoses / immunology, Polymorphism, Genetic, Fungi / isolation & purification, biology, business.industry, C-reactive protein, Fungi, Organ Transplantation, 2725 Infectious Diseases, Mycoses / genetics, Serum Amyloid P-Component, C-Reactive Protein, Infectious Diseases, Endocrinology, Mycoses, 10209 Clinic for Cardiology, biology.protein, C-Reactive Protein / genetics, Female, business, C-Reactive Protein/genetics, Fungi/isolation & purification, Mycoses/genetics, Mycoses/immunology, Organ Transplantation/adverse effects, Serum Amyloid P-Component/genetics
Published: 2015
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25. 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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26. Higher memory responses in HIV-infected and kidney transplanted patients than in healthy subjects following priming with the pandemic vaccine

Author: Cécile Delhumeau, Christian van Delden, Christophe Combescure, Claire-Anne Siegrist, Olivier F. Clerc, Paola M. Soccal, Karine Hadaya, Matthias Cavassini, Sara Meier, Laurent Kaiser, Alexandra Calmy, Michael Bel, Bernard Hirschel, Sabine Yerly, H1N1 Study Group, Swiss HIV Cohort Study (SHCS), Siegrist, CA., Posfay-Barbe, K., Meier, S., Bel, M., Grillet, S., Sealy, G., Demeules, J., Charvat, S., Verdon, M., Combescure, C., Hirschel, B., Calmy, A., Delhumeau-Cartier, C., Gabay, C., Guerne, PA., Seebach, J., Ribi, C., Villard, J., Dietrich, PY., George, AC., Favet, L., van Delden, C., Morard, I., Mentha, G., Giostra, E., Hadaya, K., Martin, PY., Soccal, P., Berney, T., Noble, S., Mohty, B., Nagy, M., Chalandon, Y., Roosnek, E., Passweg, J., Kaiser, L., Yerly, S., Thomas, Y., Wunderli, W., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., 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., Hösli, I., Kahlert, C., 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., Posfay Barbe, Klara, and Grillet, Stéphane
Subjects: Male, lcsh:Medicine, Adult, Aged, Antibodies, Viral/blood, Antibodies, Viral/immunology, Female, HIV Infections/blood, HIV Infections/immunology, Humans, Immunocompromised Host, Immunologic Memory/drug effects, Influenza Vaccines/administration & dosage, Influenza, Human/blood, Influenza, Human/immunology, Kidney Transplantation/immunology, Middle Aged, Pandemics, HIV Infections/blood/immunology, HIV Infections, ddc:616.07, Antibodies, Viral, 0302 clinical medicine, Pandemic, 030212 general & internal medicine, lcsh:Science, Prospective cohort study, Kidney transplantation, ddc:616, 0303 health sciences, Multidisciplinary, ddc:617, biology, Vaccination, Antibody titer, HIV diagnosis and management, 3. Good health, Titer, Influenza, Human/blood/immunology/prevention & control, Influenza Vaccines, Medicine, Infectious diseases, HIV clinical manifestations, Antibody, Research Article, Retrovirology and HIV immunopathogenesis, Viral diseases, 03 medical and health sciences, Immune system, Influenza, Human, medicine, Antibodies, Viral/blood/immunology, 030306 microbiology, business.industry, lcsh:R, Immunity, HIV, medicine.disease, Kidney Transplantation, Institutional repository, Immunology, biology.protein, lcsh:Q, Clinical Immunology, business, Immunologic Memory
Abstract: BACKGROUND: Memory responses require immune competence. We assessed the influence of priming with AS03-adjuvanted pandemic vaccine (Pandemrix®) on memory responses of HIV patients, kidney recipients (SOT) and healthy controls (HC). METHOD: Participants (HIV: 197, SOT: 53; HC: 156) were enrolled in a prospective study and 390/406 (96%) completed it. All had been primed in 2009/2010 with 1 (HC) or 2 (patients) doses of Pandemrix®, and were boosted with the 2010/2011 seasonal influenza vaccine. Geometric mean titres and seroprotection rates were measured 12 months after priming and 4 weeks after boosting. Primary and memory responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51) followed during 2 consecutive seasons. RESULTS: Most participants (HC: 77.8%, HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming. Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced persisting and memory responses, mainly influenced by residual antibody titers. Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2 seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients. CONCLUSIONS: Priming with 2 doses of Pandemrix® elicited persistent antibody responses and even stronger memory responses to non-adjuvanted seasonal vaccine in HIV patients than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory responses of immunocompromised patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022905.
Published: 2012

27. 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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28. 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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29. 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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30. 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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31. Resurgence of HIV infection among men who have sex with men in Switzerland: mathematical modelling study

Author: André Jeannin, A.I. van Sighem, Tracy R. Glass, Heiner C. Bucher, F. De Wolf, Daniela Bezemer, Christophe Fraser, Pietro Vernazza, Martin D. Gebhardt, S Derendinger, Beatriz Vidondo, Nicola Low, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Burton-Jeangros, C., Calmy, A., Cavassini, M., 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., von Wyl, V., Weber, R., and Yerly, S.
Subjects: Adult, Male, Cart, Sexual Behavior, HIV Infections/epidemiology, HIV Infections/transmission, Homosexuality, Male, Humans, Incidence, Models, Statistical, Prevalence, Public Health Surveillance, Switzerland/epidemiology, HIV prevention, Sexually Transmitted Diseases, Human immunodeficiency virus (HIV), lcsh:Medicine, Population Modeling, HIV Infections, Viral diseases, medicine.disease_cause, Men who have sex with men, Public health surveillance, Acquired immunodeficiency syndrome (AIDS), Medicine, lcsh:Science, Hiv transmission, Biology, Multidisciplinary, Risk behaviour, business.industry, Incidence (epidemiology), lcsh:R, Computational Biology, HIV, virus diseases, medicine.disease, AIDS, HIV epidemiology, Immunology, Infectious diseases, lcsh:Q, Public Health, Preventive Medicine, Infectious Disease Modeling, Behavioral and Social Aspects of Health, business, Switzerland, Research Article, Demography
Abstract: Background New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. Methodology/Principal Findings The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995–1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. Conclusions/Significance The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.
Published: 2012
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32. Ageing with HIV: medication use and risk for potential drug-drug interactions

Author: Marzolini, Catia, Back, David, Weber, Rainer, Furrer, Hansjakob, Cavassini, Matthias, Calmy, Alexandra, Vernazza, Pietro, Bernasconi, Enos, Khoo, Saye, Battegay, Manuel, Elzi, Luigia, Swiss HIV Cohort Study, Members, University of Zurich, Marzolini, C, Swiss HIV Cohort Study Members, Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Calmy, A., Cattacin, S., Cavassini, M., Dubs, R., Egger, M., Elzi, L., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Fux, C., Gorgievski, M., Günthard, H., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, Ch., Kaiser, L., Karrer, U., Kind, C., Klimkait, T., Ledergerber, B., Martinetti, G., Martinez, B., Müller, N., Nadal, D., Opravil, M., Paccaud, F., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., 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, Aging, Human immunodeficiency virus (HIV), HIV Infections, Pharmacology, medicine.disease_cause, 2726 Microbiology (medical), Cohort Studies, 10234 Clinic for Infectious Diseases, Antiretroviral Therapy, Highly Active, 2736 Pharmacology (medical), Drug Interactions, Pharmacology (medical), Substance Abuse, Intravenous, media_common, Medication use, Middle Aged, 3004 Pharmacology, Infectious Diseases, Tolerability, Female, Switzerland, medicine.drug, Adult, Narcotics, Microbiology (medical), Drug, medicine.medical_specialty, Anti-HIV Agents, Substance-Related Disorders, media_common.quotation_subject, 610 Medicine & health, Drug Prescriptions, Gastrointestinal Agents, Internal medicine, medicine, Humans, Aged, Aging/physiology, Anti-HIV Agents/adverse effects, Anti-HIV Agents/therapeutic use, Antiretroviral Therapy, Highly Active/adverse effects, Cardiovascular Agents/adverse effects, Cardiovascular Agents/therapeutic use, Central Nervous System Agents/adverse effects, Central Nervous System Agents/therapeutic use, Drug Prescriptions/statistics & numerical data, Follow-Up Studies, Gastrointestinal Agents/adverse effects, Gastrointestinal Agents/therapeutic use, HIV Infections/complications, HIV Infections/drug therapy, Hormones/adverse effects, Hormones/therapeutic use, Methadone/adverse effects, Methadone/therapeutic use, Narcotics/adverse effects, Narcotics/therapeutic use, Socioeconomic Factors, Substance Abuse, Intravenous/complications, Substance-Related Disorders/complications, Switzerland/epidemiology, business.industry, Cardiovascular Agents, 2725 Infectious Diseases, Antiretroviral therapy, Hormones, Ageing, Cardiovascular agent, business, Methadone, Central Nervous System Agents
Abstract: OBJECTIVES: To compare the use of co-medication, the potential drug-drug interactions (PDDIs) and the effect on antiretroviral therapy (ART) tolerability and efficacy in HIV-infected individuals according to age, ≥ 50 years or
Published: 2011
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33. Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study

Author: Lubomirov Rubin, Colombo Sara, di Iulio Julia, Ledergerber Bruno, Martinez Raquel, Cavassini Matthias, Hirschel Bernard, Bernasconi Enos, Elzi Luigia, Vernazza Pietro, Furrer Hansjakob, Günthard Huldrych F, Telenti Amalio, Swiss HIV Cohort Study, University of Zurich, Telenti, A, 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., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, HF., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Karrer, U., Kind, C., Klimkait, T., Ledergerber, B., Martinetti, G., Müller, N., Nadal, D., Paccaud, F., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., de Tejada BM., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Adult, Genetic Markers, Male, medicine.medical_specialty, Efavirenz, Anti-HIV Agents, HIV Infections, 610 Medicine & health, Medication Adherence, Cohort Studies, 10234 Clinic for Infectious Diseases, Major Articles and Brief Reports, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Abacavir, Antiretroviral Therapy, Highly Active, Internal medicine, Humans, Immunology and Allergy, Medicine, 030212 general & internal medicine, 030304 developmental biology, 0303 health sciences, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/adverse effects, Antiretroviral Therapy, Highly Active/adverse effects, Female, HIV Infections/drug therapy, Medication Adherence/statistics & numerical data, Middle Aged, Pharmacogenetics, business.industry, Hazard ratio, virus diseases, Lopinavir, 2725 Infectious Diseases, 3. Good health, Discontinuation, Atazanavir, Infectious Diseases, chemistry, Immunology, Cohort, 2723 Immunology and Allergy, Ritonavir, business, medicine.drug
Abstract: BACKGROUND: Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care. METHODS: A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models. RESULTS: During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001). CONCLUSIONS: Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting.
Published: 2011
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34. 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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35. 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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36. Predictors for the Emergence of the 2 Multi-nucleoside/nucleotide Resistance Mutations 69 Insertion and Q151M and their Impact on Clinical Outcome in the Swiss HIV Cohort Study

Author: Sabine Yerly, Alexandra U. Scherrer, Thomas Klimkait, Beda Joos, Bruno Ledergerber, Viktor von Wyl, Philippe Bürgisser, Jürg Böni, Huldrych F. Günthard, University of Zurich, 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., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Karrer, U., Kind, C., Klimkait, T., Ledergerber, B., Martinetti, G., Müller, N., Nadal, D., Paccaud, F., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., de Tejada BM., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: 10028 Institute of Medical Virology, HIV Infections, medicine.disease_cause, Cohort Studies, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Risk Factors, Cause of Death, Immunology and Allergy, 030212 general & internal medicine, Didanosine, Cause of death, ddc:616, 0303 health sciences, Mutation, biology, Mortality rate, 3. Good health, Treatment Outcome, Infectious Diseases, Anti-Retroviral Agents, Lentivirus, 2723 Immunology and Allergy, Switzerland, Cohort study, medicine.drug, medicine.medical_specialty, Anti-HIV Agents/pharmacology, Anti-Retroviral Agents/pharmacology, Anti-Retroviral Agents/therapeutic use, Case-Control Studies, Didanosine/pharmacology, Drug Resistance, Multiple, Viral/genetics, HIV Infections/drug therapy, HIV Infections/mortality, HIV-1/drug effects, HIV-1/genetics, Humans, Logistic Models, Switzerland/epidemiology, Anti-HIV Agents, 610 Medicine & health, Major Articles and Brief Reports, 03 medical and health sciences, Drug Resistance, Multiple, Viral, Internal medicine, medicine, 030306 microbiology, business.industry, Case-control study, 2725 Infectious Diseases, Odds ratio, biology.organism_classification, Immunology, HIV-1, 570 Life sciences, business
Abstract: The 69 insertion and Q151M mutations are multi-nucleoside/nucleotide resistance mutations (MNR). The prevalence among 4078 antiretroviral therapy (ART)-experienced individuals was
Published: 2011

37. 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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38. Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study

Author: S, Franceschi, M, Lise, G M, Clifford, M, Rickenbach, F, Levi, M, Maspoli, C, Bouchardy, S, Dehler, G, Jundt, S, Ess, A, Bordoni, I, Konzelmann, H, Frick, L, Dal Maso, L, Elzi, H, Furrer, A, Calmy, M, Cavassini, B, Ledergerber, O, Keiser, S, Yerly, University of Zurich, Franceschi, S, Swiss HIV Cohort Study, Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Calmy, A., Cavassini, M., Dubs, R., Egger, M., Elzi, L., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, HF., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Karrer, U., Kind, C., Klimkait, T., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., 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., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Oncology, Male, Cancer Research, Skin Neoplasms, HAART, Epidemiology, Prevalence, HIV Infections, 10234 Clinic for Infectious Diseases, Neoplasms/*epidemiology, Cohort Studies, Switzerland/epidemiology, Sarcoma, Kaposi/epidemiology, immune system diseases, hemic and lymphatic diseases, Antiretroviral Therapy, Highly Active, Neoplasms, 1306 Cancer Research, Lymphoma, Non-Hodgkin/*epidemiology, ddc:616, Incidence (epidemiology), Incidence, Lymphoma, Non-Hodgkin, virus diseases, Chromosome Mapping, Middle Aged, Acquired Immunodeficiency Syndrome/drug therapy, Adult, Aged, Antiretroviral Therapy, Highly Active/adverse effects, Drug Administration Schedule, Female, HIV Infections/drug therapy, Humans, Lymphoma, Non-Hodgkin/epidemiology, Neoplasms/epidemiology, Skin Neoplasms/epidemiology, 2730 Oncology, Switzerland, Cohort study, medicine.medical_specialty, 610 Medicine & health, Antiretroviral Therapy, Highly Active/*adverse effects, Acquired immunodeficiency syndrome (AIDS), Internal medicine, 10049 Institute of Pathology and Molecular Pathology, medicine, Anal cancer, Kaposi's sarcoma, Sarcoma, Kaposi, Acquired Immunodeficiency Syndrome, business.industry, HIV, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), medicine.disease, Non-Hodgkin's lymphoma, age, Immunology, incidence rates, Skin cancer, business
Abstract: BACKGROUND: The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy. METHODS: We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20,615, 17,690, and 15,410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods. RESULTS: Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkin's lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population. CONCLUSIONS: Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.
Published: 2010
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39. Infrequent replication of parvovirus B19 and erythrovirus genotypes 2 and 3 among HIV-infected patients with chronic anemia

Author: Thanh Dang, Rainer Weber, Enos Bernasconi, Patrick Schmid, Bernard Hirschel, Andri Rauch, Luigia Elzi, Alexandra Calmy, Cécile Delhumeau, Tristan Ferry, Pascal Meylan, University of Zurich, Ferry, 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., Fischer, M., Flepp, M., Fontana, A., Francioli P, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, HF., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Karrer, U., Kind, C., Klimkait, T., Ledergerber, B., Martinetti, G., Müller, N., Nadal, D., Paccaud, F., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., de Tejada BM., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., Weber R, R., and Yerly, S.
Subjects: Adult, Male, Microbiology (medical), Anemia, HIV Infections, 610 Medicine & health, Virus Replication, Polymerase Chain Reaction, Virus, 2726 Microbiology (medical), law.invention, Cohort Studies, Parvoviridae Infections, 10234 Clinic for Infectious Diseases, Blood serum, law, hemic and lymphatic diseases, Parvovirus B19, Human, medicine, Humans, Parvovirus B19, Human/isolation & purification/ physiology, Anemia/blood, Anemia/complications, Chronic Disease, DNA, Viral/blood, Erythrovirus/isolation & purification, Erythrovirus/physiology, Female, HIV Infections/blood, HIV Infections/complications, Middle Aged, Parvoviridae Infections/blood, Parvoviridae Infections/complications, Parvovirus B19, Human/isolation & purification, Parvovirus B19, Human/physiology, Parvoviridae Infections/blood/complications/virology, Anemia/blood/complications/ virology, Polymerase chain reaction, ddc:616, Parvoviridae, Erythrovirus, biology, business.industry, Parvovirus, HIV Infections/blood/complications/ virology, virus diseases, 2725 Infectious Diseases, medicine.disease, biology.organism_classification, Virology, Infectious Diseases, DNA, Viral, Immunology, Viral disease, Erythrovirus/isolation & purification/ physiology, business
Abstract: We investigated the role that erythroviruses (parvovirus B19 and erythrovirus genotypes 2 and 3) play in the lives of immunosuppressed HIV-infected patients with chronic anemia. We screened the serum samples of 428 patients by specific ultrasensitive real-time polymerase chain reaction assay. Sixteen patients had circulating DNA, with no apparent clinical impact. Erythrovirus-associated anemia is an extremely rare event in HIV-infected patients.
Published: 2010
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40. HIV-1 reverse transcriptase connection domain mutations: dynamics of emergence and implications for success of combination antiretroviral therapy

Author: Viktor, von Wyl, Maryam, Ehteshami, Lisa M, Demeter, Philippe, Bürgisser, Monique, Nijhuis, Jori, Symons, Sabine, Yerly, Jürg, Böni, Thomas, Klimkait, Rob, Schuurman, Bruno, Ledergerber, Matthias, Götte, Huldrych F, Günthard, S, Yerly, University of Zurich, von Wyl, V, 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., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, HF., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Karrer, U., Kind, C., Klimkait, T., Ledergerber, B., Martinetti, G., Müller, N., Nadal, D., Paccaud, F., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., de Tejada BM., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Microbiology (medical), medicine.medical_specialty, Combination therapy, Genotype, Anti-HIV Agents, 610 Medicine & health, Drug resistance, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, 03 medical and health sciences, Zidovudine, 0302 clinical medicine, Molecular genetics, Drug Resistance, Viral, medicine, Humans, 030212 general & internal medicine, 030304 developmental biology, Retrospective Studies, 0303 health sciences, biology, Nucleoside analogue, Base Sequence, business.industry, Lamivudine, 2725 Infectious Diseases, biology.organism_classification, Virology, Reverse transcriptase, HIV Reverse Transcriptase, 3. Good health, Infectious Diseases, Lentivirus, Mutation, HIV-1, Drug Therapy, Combination, business, medicine.drug, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/therapeutic use, HIV Reverse Transcriptase/genetics, HIV Reverse Transcriptase/metabolism, HIV-1/drug effects, HIV-1/enzymology
Abstract: BACKGROUND: Factors promoting the emergence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) connection domain mutations and their effect on antiretroviral therapy (ART) are still largely undetermined. We investigated this matter by analyzing genotypic resistance tests covering 400 amino acid positions in the RT of HIV-1 subtype B viruses and corresponding treatment histories and laboratory measurements. METHODS: The emergence of connection domain mutations was studied in 334 patients receiving monotherapy or dual therapy with thymidine analogues at the time of the genotypic resistance test. Response to subsequent combination ART (cART) was analyzed using Cox regression for 291 patients receiving unboosted protease inhibitors. Response was defined by ever reaching an HIV RNA level
Published: 2010

41. Incidence and outcome of progressive multifocal leukoencephalopathy over 20 years of the Swiss HIV Cohort Study

Author: Luigia Elzi, Pietro Vernazza, Christian Garzoni, Hans H. Hirsch, Matthias Cavassini, Christoph A Fux, Nicolas J. Mueller, Enos Bernasconi, Nina Khanna, Manuel Battegay, University of Zurich, 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., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Fux, C., Gorgievski, M., Günthard, H., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Karrer, U., Kind, C., Klimkait, T., Ledergerber, B., Martinetti, G., Martinez, B., Müller, N., Nadal, D., Opravil, M., Paccaud, F., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., 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: Adult, Male, Microbiology (medical), Pathology, medicine.medical_specialty, Anti-HIV Agents, 610 Medicine & health, HIV Infections, Gastroenterology, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, Cohort Studies, Interquartile range, Antiretroviral Therapy, Highly Active, Internal medicine, medicine, Humans, Survival analysis, business.industry, Incidence, Mortality rate, Incidence (epidemiology), Progressive multifocal leukoencephalopathy, Hazard ratio, Leukoencephalopathy, Progressive Multifocal, virus diseases, 2725 Infectious Diseases, medicine.disease, Confidence interval, CD4 Lymphocyte Count, Treatment Outcome, Infectious Diseases, Female, business, Anti-HIV Agents/therapeutic use, HIV Infections/complications, HIV Infections/immunology, Leukoencephalopathy, Progressive Multifocal/epidemiology, Leukoencephalopathy, Progressive Multifocal/mortality, Switzerland/epidemiology, Switzerland, Cohort study
Abstract: BACKGROUND: We investigated the incidence and outcome of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected individuals before and after the introduction of combination antiretroviral therapy (cART) in 1996. METHODS: From 1988 through 2007, 226 cases of PML were reported to the Swiss HIV Cohort Study. By chart review, we confirmed 186 cases and recorded all-cause and PML-attributable mortality. For the survival analysis, 25 patients with postmortem diagnosis and 2 without CD4+ T cell counts were excluded, leaving a total of 159 patients (89 before 1996 and 70 during 1996-2007). RESULTS: The incidence rate of PML decreased from 0.24 cases per 100 patient-years (PY; 95% confidence interval [CI], 0.20-0.29 cases per 100 PY) before 1996 to 0.06 cases per 100 PY (95% CI, 0.04-0.10 cases per 100 PY) from 1996 onward. Patients who received a diagnosis before 1996 had a higher frequency of prior acquired immunodeficiency syndrome-defining conditions (P = .007) but similar CD4+ T cell counts (60 vs. 71 cells/microL; P = .25), compared with patients who received a diagnosis during 1996 or thereafter. The median time to PML-attributable death was 71 days (interquartile range, 44-140 days), compared with 90 days (interquartile range, 54-313 days) for all-cause mortality. The PML-attributable 1-year mortality rate decreased from 82.3 cases per 100 PY (95% CI, 58.8-115.1 cases per 100 PY) during the pre-cART era to 37.6 cases per 100 PY (95% CI, 23.4.-60.5 cases per 100 PY) during the cART era. In multivariate models, cART was the only factor associated with lower PML-attributable mortality (hazard ratio, 0.18; 95% CI, 0.07-0.50; P < .001), whereas all-cause mortality was associated with baseline CD4+ T cell count (hazard ratio per increase of 100 cells/microL, 0.52; 95% CI, 0.32-0.85; P = .010) and cART use (hazard ratio, 0.37; 95% CI, 0.19-0.75; P = .006). CONCLUSIONS: cART reduced the incidence and PML-attributable 1-year mortality, regardless of baseline CD4+ T cell count, whereas overall mortality was dependent on cART use and baseline CD4+ T cell count.
Published: 2009
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42. 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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43. 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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44. 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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45. Population pharmacokinetic modelling and evaluation of different dosage regimens for darunavir and ritonavir in HIV-infected individuals

Author: Arab-Alameddine M, Lubomirov R, Fayet-Mello A, Aouri M, Rotger M, Buclin T, Widmer N, Gatri M, Ledergerber B, Rentsch K, Cavassini M, Panchaud A, Guidi M, Telenti A, La, Décosterd, Chantal Csajka, Hiv, Swiss Cohort Study, 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., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Karrer, U., Kind, C., Klimkait, T., Ledergerber, B., Martinetti, G., Müller, N., Nadal, D., Paccaud, F., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., de Tejada BM., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Csajka, C
Subjects: Microbiology (medical), Adult, Male, Anti-HIV Agents, Population, 610 Medicine & health, HIV Infections, Pharmacology, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, Cmin, Plasma, Young Adult, Pharmacokinetics, immune system diseases, 540 Chemistry, medicine, 2736 Pharmacology (medical), Humans, Pharmacology (medical), Drug Interactions, education, Darunavir, 10038 Institute of Clinical Chemistry, Aged, education.field_of_study, Sulfonamides, Ritonavir, business.industry, virus diseases, Lopinavir, 2725 Infectious Diseases, Middle Aged, NONMEM, Regimen, 3004 Pharmacology, Infectious Diseases, Drug Therapy, Combination, Female, business, medicine.drug
Abstract: OBJECTIVES: Darunavir is a protease inhibitor that is administered with low-dose ritonavir to enhance its bioavailability. It is prescribed at standard dosage regimens of 600/100 mg twice daily in treatment-experienced patients and 800/100 mg once daily in naive patients. A population pharmacokinetic approach was used to characterize the pharmacokinetics of both drugs and their interaction in a cohort of unselected patients and to compare darunavir exposure expected under alternative dosage regimens. METHODS: The study population included 105 HIV-infected individuals who provided darunavir and ritonavir plasma concentrations. Firstly, a population pharmacokinetic analysis for darunavir and ritonavir was conducted, with inclusion of patients' demographic, clinical and genetic characteristics as potential covariates (NONMEM(®)). Then, the interaction between darunavir and ritonavir was studied while incorporating levels of both drugs into different inhibitory models. Finally, model-based simulations were performed to compare trough concentrations (Cmin) between the recommended dosage regimen and alternative combinations of darunavir and ritonavir. RESULTS: A one-compartment model with first-order absorption adequately characterized darunavir and ritonavir pharmacokinetics. The between-subject variability in both compounds was important [coefficient of variation (CV%) 34% and 47% for darunavir and ritonavir clearance, respectively]. Lopinavir and ritonavir exposure (AUC) affected darunavir clearance, while body weight and darunavir AUC influenced ritonavir elimination. None of the tested genetic variants showed any influence on darunavir or ritonavir pharmacokinetics. The simulations predicted darunavir Cmin much higher than the IC50 thresholds for wild-type and protease inhibitor-resistant HIV-1 strains (55 and 550 ng/mL, respectively) under standard dosing in >98% of experienced and naive patients. Alternative regimens of darunavir/ritonavir 1200/100 or 1200/200 mg once daily also had predicted adequate Cmin (>550 ng/mL) in 84% and 93% of patients, respectively. Reduction of darunavir/ritonavir dosage to 600/50 mg twice daily led to a 23% reduction in average Cmin, still with only 3.8% of patients having concentrations below the IC50 for resistant strains. CONCLUSIONS: The important variability in darunavir and ritonavir pharmacokinetics is poorly explained by clinical covariates and genetic influences. In experienced patients, treatment simplification strategies guided by drug level measurements and adherence monitoring could be proposed.

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