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1. Gender differences in the use of cardiovascular interventions in HIV?positive persons; the D:A:D Study

Author

Hatleberg, Camilla I., Ryom, Lene, El?Sadr, Wafaa, Mocroft, Amanda, Reiss, Peter, De Wit, Stephane, Dabis, Francois, Pradier, Christian, Monforte, Antonella D'Arminio, Kovari, Helen, Law, Matthew, Lundgren, Jens D., Sabin, Caroline A., Calvo, G, Bonnet, F, Kirk, O, Morfeldt, L, Weber, R, Lind?Thomsen, A, Brandt, R Salbøl, Hillebreght, M, Zaheri, S, Wit, Fwnm, 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, Meer, Jtm, Godfried, Mh, Poll, T, Nellen, Fjb, Geerlings, Se, Vugt, M, Pajkrt, D, Bos, Jc, Wiersinga, Wj, Valk, M, Goorhuis, A, Hovius, Jw, Eden, J, Henderiks, A, Hes, Amh, Mutschelknauss, M, Nobel, He, Pijnappel, Fjj, Jurriaans, S, Back, Nkt, Zaaijer, Hl, Berkhout, B, Cornelissen, Mte, Schinkel, Cj, Thomas, Xv, Ziekenhuis, A De Ruyter, Berge, M, Stegeman, A, Baas, S, De Looff, L Hage, Ziekenhuis, C, Pronk, Mjh, Ammerlaan, Hsm, Munnik, E, Tjhie, J, Wegdam, Mca, Deiman, B, Scharnhorst, V, Weijsenfeld, Am, Ende, Me, Gorp, Ecm, Schurink, Cam, Nouwen, Jl, Verbon, A, Rijnders, Bja, Bax, Hi, Feltz, M, Bassant, N, Beek, Jea, Vriesde, M, Zonneveld, Lm, Oude?Lubbers, A, Berg?Cameron, Hj, Bruinsma?Broekman, Fb, Groot, J, Man, M Zeeuw?De, Boucher, Cab, Koopmans, Mpg, Kampen, Jja, Pas, Sd, Driessen, Gja, Rossum, Amc, Knaap, Lc, Flevoziekenhuis, E, Branger, J, Rijkeboer?Mes, A, Schippers, Ef, Ijperen, Jm, Geilings, J, Hut, G, Franck, Pfh, Eeden, A, Brokking, W, Groot, M, Elsenburg, Ljm, Damen, M, Isala, Is, Groeneveld, Php, Bouwhuis, Jw, Berg, Jf, Hulzen, Agw, Bliek, Gl, Bor, Pcj, Bloembergen, P, Wolfhagen, Mjhm, Ruijs, Gjhm, Kroon, Fp, Boer, Mgj, Bauer, Mp, Jolink, H, Vollaard, Am, Dorama, W, Holten, N, Claas, Ecj, Wessels, E, Den Hollander, Jg, Pogany, K, Roukens, A, Kastelijns, M, Smit, Jv, Smit, E, Struik?Kalkman, D, Tearno, C, Bezemer, M, Niekerk, T, Pontesilli, O, Lowe, Sh, Lashof, Aml Oude, Posthouwer, D, Ackens, Rp, Schippers, J, Vergoossen, R, Weijenberg?Maes, B, Loo, Ihm, Havenith, Tra, Leyten, Ems, Gelinck, Lbs, Hartingsveld, A, Meerkerk, C, Wildenbeest, Gs, Mutsaers, Jaem, Jansen, Cl, Mulder, Jw, Vrouenraets, Sme, Lauw, Fn, Broekhuizen, Mc, Paap, H, Vlasblom, Dj, Smits, Phm, Weijer, S, Moussaoui, R El, Bosma, As, Vonderen, Mga, Houte, Dpf, Kampschreur, Lm, Dijkstra, K, Faber, S, Weel, J, Kootstra, Gj, Delsing, Ce, De Plas, M Burg?Van, Heins, H, Lucas, E, Kortmann, W, Twillert¤, G, Stuart, Jwt Cohen, Diederen, Bmw, Pronk, D, Truijen?Oud, Fa, Reijden, Wa, Jansen, R, Brinkman¤, K, Berk, Gel, Blok, Wl, Frissen, Phj, Lettinga, Kd, Schouten, Wem, Veenstra, J, Brouwer, Cj, Geerders, Gf, Hoeksema, K, Kleene, Mj, Meché, Ib, Spelbrink, M, Sulman, H, Toonen, Ajm, Wijnands, S, Kwa, D, Witte, E, Koopmans, Pp, Keuter, M, Ven, Ajam, Hofstede, Hjm, Dofferhoff, Asm, Crevel, R, Albers, M, Bosch, Mew, Grintjes?Huisman, Kjt, Zomer, Bj, Stelma, Ff, Rahamat?Langendoen, J, Burger, D, Richter, C, Gisolf, Eh, Hassing, Rj, Beest, G, Van Bentum, Phm, Langebeek, N, Tiemessen, R, Swanink, Cma, Lelyveld, Sfl, Soetekouw, R, Hulshoff, N, Prijt, Lmm, Swaluw, J, Bermon, N, Herpers, Bl, Veenendaal, D, Verhagen, Dwm, Wijk, M, Brouwer, Ae, Kuipers, M, Santegoets, Rmwj, Ven, B, Marcelis, Jh, Buiting, Agm, Kabel, Pj, Bierman, Wfw, Scholvinck, H, Wilting, Kr, Stienstra, Y, Meulen, Pa, Weerd, Da, Ludwig?Roukema, J, Niesters, Hgm, Riezebos?Brilman, A, Leer?Buter, Cc, Knoester, M, Hoepelman, Aim, Mudrikova, T, Ellerbroek, Pm, Oosterheert, Jj, Arends, Je, Barth, Re, Wassenberg, Mwm, Schadd, Em, Elst?Laurijssen, Dhm, Oers?Hazelzet, Eeb, Vervoort, S, Berkel, M, Schuurman, R, Verduyn?Lunel, F, Wensing, Amj, Peters, Ejg, Agtmael, Ma, Bomers, M, Vocht, J, Heitmuller, M, Laan, Lm, Pettersson, Am, Ang, Cw, Geelen, Spm, Wolfs, Tfw, Bont, Lj, Bezemer, Do, Sighem, Ai, Boender, Ts, Jong, A, Bergsma, D, Hoekstra, P, Lang, A, Grivell, S, Jansen, A, Rademaker, Mj, Raethke, M, Meijering, R, Schnörr, S, Groot, L, Akker, M, Bakker, Y, Claessen, E, Berkaoui, A El, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, 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, E Lenaud Et A., 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, 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, Laut, K Grønborg, 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, J?P, Girard, P?M, 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, 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, Roldan, E Quiros, 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, Sulekova, L Fontanelli, Iaiani, G, Latini, A, Mastrorosa, I, Plazzi, Mm, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Del Vecchio, R Fontana, 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, Hc, 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, De Tejada, B Martinez, 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, and Yerly, S

Subjects
Statistics, Care and treatment, Analysis, Demographic aspects, HIV patients -- Statistics -- Care and treatment -- Demographic aspects, Cardiovascular surgery -- Statistics -- Demographic aspects, Medical care utilization -- Statistics -- Demographic aspects, Disease sex factors -- Analysis, Medical care -- Utilization, Cardiovascular system -- Surgery, Sex factors in disease -- Analysis
Abstract

Introduction HIV?positive individuals are known to be at increased risk of cardiovascular disease (CVD) compared to the general population, partly due to an increased prevalence of some CVD risk factors, [...], : Introduction: 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.

Published
2018
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2. Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy

Author

Wijting, Ingeborg, Wit, FWNM, Rokx, Casper, Leyten, EMS, Lowe, SH, Brinkman, K, Bierman, WFW, van Kasteren, MEE, Postma, AM, Bloemen, Vera, Bouchtoubi, Ghariba, Hoepelman, AIM, Ende, Marchina, Reiss, P, Rijnders, Bart, Wijting, Ingeborg, Wit, FWNM, Rokx, Casper, Leyten, EMS, Lowe, SH, Brinkman, K, Bierman, WFW, van Kasteren, MEE, Postma, AM, Bloemen, Vera, Bouchtoubi, Ghariba, Hoepelman, AIM, Ende, Marchina, Reiss, P, and Rijnders, Bart

Published
2019

5. 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, 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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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7. Erythrocyte Inosine Triphosphatase Activity Is Decreased in HIV-Seropositive Individuals

Author

Bierau, J, Bakker, Johan, Schippers, JA, Grashorn, JAC, Lindhout, M, Lowe, SH, Paulussen, ADC, Verbon, Annelies, Bierau, J, Bakker, Johan, Schippers, JA, Grashorn, JAC, Lindhout, M, Lowe, SH, Paulussen, ADC, and Verbon, Annelies

Abstract

Background: Inosine triphosphatase (ITPase) is encoded by the polymorphic gene ITPA and maintains low intracellular levels of the inosine nucleotides ITP and dITP. The most frequently reported polymorphisms are ITPA c.94C>A (rs 1127354) and ITPA c. 124+21 A>C (rs7270101). Some nucleoside-analogues used in the treatment of HIV-seropositive (HIV+) patients are potential substrates for ITPase. Therefore, the frequency of ITPA SNPs and ITPase activity were studied in a population of HIV+-patients. Methods: The study population consisted of 222 patients, predominantly Caucasian males, >95% using HAART. Erythrocyte ITPase activity was determined by measuring the formation of IMP from ITP. ITPA genotype was determined by sequencing genomic DNA. Distribution of ITPase activity, genotype-phenotype correlation and allele frequencies were compared to 198 control subjects. The effect of nucleoside analogues on ITPase activity was studied using lymphoblastic T-cell cultures and human recombinant I Results: No difference was observed in the allele frequencies between the HIV+-cohort (+/- HAART) and the control population. HIV+ carriers of the wild type and ITPA c.94C>A had significantly lower ITPase activities than control subjects with the same genotype (p<0.005). This was not observed in ITPA c. 124+21 A>C carriers. Nucleoside analogues did not affect ITPase activity in cell culture and human recombinant ITPase. Conclusion: ITPA population genetics were identical in HIV+ and control popu

Published
2012

8. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1 infected individuals with virological failure to all three antiretroviral-drug classes

Author

Ledergerber, B, Lundgren, Jd, Walker, As, Sabin, C, Justice, A, Reiss, P, Mussini, C, Wit, F, d'Arminio Monforte, A, Weber, R, Fusco, G, Staszewski, S, Law, M, Hogg, R, Lampe, F, Gill, Mj, Castelli, Francesco, Phillips, An, Rooney, P. q, Taylor, S. q, Couldwell, D. r, Austin, D. s, Block, M. s, Clemons, J. s, Finlayson, R. s, Petoumenos, K. s, Quan, D. s, Smith, D. s, O'Connor, C. t, Gorton, C. t, Allen, D. u, Mulhall, B. u, Mutimer, K. v, Keeffe, N. v, Cooper, D. w, Carr, A. w, Miller, J. w, Pell, C. w, Ellis, D. x, Baker, D. y, Kidd, J. y, Mcfarlane, R. y, Liang, M. T. z, Brown, Aa, K., Huffam, Ab, S., Savage, Ab, J., Morgan, Knibbs, Ab, P., Sowden, Ac, D., Walker, Ac, A., Orth, Ad, D., Lister, Ad, G., Chuah, Ae, J., Fankhauser, Ae, W., Dickson, Ae, B., Bradford, Af, D., Wilson, Af, C., Ree, Ag, H., Magon, Anderson, Ah, J., Moore, Ah, R., Russell, Ah, D., Mcgovern, Ah, G., Mcnair, Bal, Fairley, Ah, K., Roth, Ai, N., Ai, B., Strecker, Ai, S., Ai, D., Wood, Ai, H., Mijch, Aj, A., Hoy, Aj, J., Pierce, Mccormack, Aj, C., Watson, Aj, K., Medland, Ak, N., Daye, Al, J., Mallal, Am, S., French, Am, M., Skett, Am, J., Maxwel, Am, D., Cain, Am, A., Montroni, An, M., Scalise, An, G., Costantini, An, A., Giacometti, Tirelli, Ao, U., Nasti, Ao, G., Pastore, Ap, G., Ladisa, Ap, N., Perulli, M. L., Ap, Suter, Aq, F., Arici, Aq, C., Maggiolo, Chiodo, Ar, F., Gritti, F. M., Ar, Colangeli, Ar, V., Fiorini, Ar, C., Guerra, Ar, L., Carosi, As, G., Cadeo, G. P., As, Minardi, As, C., Vangi, As, D., Paraninfo, Casari, As, S., Pan, As, A., Patroni, Torti, Quiros, Roldan, As, E., Tomasoni, As, L., Moretti, As, F., Nasta, As, P., Uccelli, M. C., As, Bertelli, Rizzardini, At, G., Migliorino, At, M., Abeli, At, C., Manconi, P. E., Au, Piano, Au, P., Ferraro, Av, T., Scerbo, Av, A., Pizzigallo, Aw, E., Ricci, Aw, F., Santoro, Ax, D., Pusterla, Ax, L., Carnevale, Ay, G., Galloni, Ay, D., Viganò, Az, P., Mena, Az, M., Ghinelli, Ba, F., Sighinolfi, Ba, L., Leoncini, Bb, F., Mazzotta, Pozzi, Bb, M., Caputo, Lo, Bb, S., Angarano, Bc, G., Grisorio, Bc, B., Ferrara, Bc, S., Grima, Bd, P., Tundo, Pagano, Be, G., Piersantelli, Be, N., Alessandrini, Be, A., Piscopo, Be, R., Toti, Bf, M., Chigiotti, Bf, S., Soscia, Bg, F., Tacconi, Bg, L., Orani, Bh, A., Perini, Bh, P., Nigro, Bh, M., Scasso, Bi, A., Vincenti, Scalzini, Bj, A., Fibbia, Bj, G., Moroni, Bk, M., Lazzarin, Bk, A., Cargnel, Vigevani, G. M., Bk, Caggese, Bk, L., Tordato, Bk, F., Novati, Bk, R., Galli, Merli, Bk, S., Pastecchia, Bk, C., Moioli, Esposito, Bl, R., Abrescia, Bm, N., Chirianni, Bm, A., Izzo, Bm, C., Piazza, Bm, M., Marco, De, Montesarchio, Bm, V., Manzillo, Bm, E., Nappa, Bm, S., Colomba, Bn, A., Abbadessa, Bn, V., Prestileo, Bn, T., Mancuso, Bn, S., Ferrari, Bo, C., Pzzaferri, Bo, P., Filice, Bp, G., Minoli, Bp, L., Bruno, Bp, R., Maserati, Bp, S., Tinelli, Bp, C., Pauluzzi, Bq, S., Baldelli, Bq, F., Petrelli, Br, E., Cioppi, Br, A., Alberici, Bs, F., Ruggieri, Bs, A., Menichetti, Bt, F., Martinelli, Bt, C., Stefano, De, Bu, C., Gala, La, Bu, A., Zauli, Bv, T., Ballardini, Bv, G., Magnani, Bw, G., Ursitti, M. A., Bw, Arlotti, Bx, M., Ortolani, Bx, P., Ortona, By, L., Dianzani, By, F., Ippolito, By, G., Antinori, Bz, A., Antonucci, Bz, G., D'Elia, Bz, S., Narciso, Bz, P., Petrosillo, Bz, N., Vullo, Bz, V., Luca, De, Del, Forno, Bz, L., Zaccarelli, Bz, M., Longis, De, Ciardi, D'Offizi, Noto, Lichtner, Capobianchi, M. R., Bz, Girardi, Bz, E., Pezzotti, Rezza, Mura, M. S., Ca, Mannazzu, Ca, M., Caramello, Cb, P., Sinicco, Cb, A., Soranzo, M. L., Cb, Gennero, Cb, L., Sciandra, Cb, M., Salassa, Cb, B., Grossi, P. A., Cc, Basilico, Cc, C., Poggio, Cd, A., Bottari, Cd, G., Raise, Ce, E., Pasquinucci, Ce, S., Lalla, De, Cf, F., Tositti, Cf, G., Resta, Cg, F., Chimienti, Cg, A., Lepri, Cozzi, Ch, A., Bachmann, Fb, S., Battegay, Fb, M., Bernasconi, Fb, E., Bucher, Fb, H., Bürgisser, Fb, P., Cattacin, Egger, Erb, Fierz, Fb, W., Fischer, Flepp, Fontana, Fb, A., Francioli, Furrer, H. J., Fb, Gorgievski, Günthard, Hirschel, Fb, B., Kaiser, Fb, L., Kind, Fb, C., Klimkait, Fb, T., Lauper, Fb, U., Opravil, Paccaud, Fb, F., Pantaleo, Fb, G., Perrin, Piffaretti, J. C., Fb, Rickenbach, Rudin, Schüpbach, Fb, J., Speck, Fb, R., Tarr, Telenti, Trkola, Vernazza, Yerly, Wolf, De, Ci, F., Van, Sighem, A. I., Ci, Van, Valkengoed, Ci, I., Gras, Ci, L., Bronsveld, Ci, W., Veldkamp, Ci, A., Prins, J. M., Cj, Bos, J. C., Cj, Schattenkerk, Eeftinck, J. K. M., Cj, Godfried, M. H., Cj, Lange, J. M. A., Cj, Lowe, S. H., Cj, van der Meer, J. T. M., Cj, Nellen, F. J. B., Cj, Pogany, Cj, K., van der Poll, Cj, T., Ruys, T. A., Cj, Sankatsing, Cj, S., van der Valk, Cj, M., Van, Vonderen, M. G. A., Cj, Wit, F. W. M. N., Cj, Van, Eeden, Cj, A., Ten, Veen, J. H., Cj, Van, Dam, P. S., Cj, Hillebrand, Haverkort, M. E., Cj, Brinkman, Frissen, P. H. J., Cj, Weigel, H. M., Cj, Mulder, J. W., Cj, Van, Gorp, E. C. M., Cj, Meenhorst, P. L., Cj, Mairuhu, A. T. A., Cj, Veenstra, Cj, J., Danner, S. 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M., Cs, Claas, H. C. J., Cs, Schreij, Ct, G., van de Geest, Ct, S., Verbon, Ct, A., Bruggeman, C. A. M. V. A., Ct, Goossens, V. J., Ct, Koopmans, P. P., Cu, Telgt, Cu, M., van der Ven, A. J. A. M., Cu, Burger, D. M., Cu, Hugen, P. W. H., Cu, Galama, J. M. D., Cu, Poort, Y. A. G. M., Cu, van der Ende, M. E., Cv, Gyssens, I. C., Cv, Marie, De, Cv, S., Nouwen, J. L., Cv, Niesters, M. G., Cv, Osterhaus, A. D. M. E., Cv, Schutten, Cv, M., Juttmann, J. R., Cw, Buiting, A. G. M., Cw, Swaans, C. A. M., Cw, Schneider, M. M. E., Cx, Bonten, M. J. M., Cx, Borleffs, J. C. C., Cx, Hoepelman, I. M., Cx, Jaspers, C. A. J. J., Cx, Schouten, Cx, I., Schurink, C. A. M., Cx, Boucher, C. A. B., Cx, Schuurman, Cx, R., Blok, W. L., Cy, Groeneveld, P. H. P., Cz, Boel, Da, E., Jansz, A. 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A., Fb, Lipman, Ey, J., Read, Ey, R., Ez, F., Riccio, Fa, G., Borghi, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Infectious diseases, Global Health, Other departments, Public and occupational health, General Internal Medicine, Center of Experimental and Molecular Medicine, Ledergerber, B, Lundgren, Jd, Walker, A, Sabin, C, Justice, A, Reiss, P, Mussini, C, Wit, F, Monforte, Ad, Weber, R, Fusco, G, Staszewski, S, Law, M, Hogg, R, Lampe, F, Gill, Mj, Castelli, F, Phillips, An, Fusco, Gp, Rooney, P, Taylor, S, Couldwell, D, Austin, D, Block, M, Clemons, J, Finlayson, R, Petoumenos, K, Quan, D, Smith, D, O'Connor, C, Gorton, C, Allen, D, Mulhall, B, Mutimer, K, Keeffe, N, Cooper, D, Carr, A, Miller, J, Pell, C, Ellis, D, Baker, D, Kidd, J, Mcfarlane, R, Liang, Mt, Brown, K, Huffam, S, Savage, J, Morgan, S, Knibbs, P, Sowden, D, Orth, D, Lister, G, Chuah, J, Fankhauser, W, Dickson, B, Bradford, D, Wilson, C, Ree, H, Magon, H, Anderson, J, Moore, R, 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Lepri, Ac, Bachmann, S, Battegay, M, Bernasconi, E, Bucher, H, Burgisser, P, Cattacin, S, Egger, M, Erb, P, Fierz, W, Fischer, M, Flepp, M, Fontana, A, Francioli, P, Furrer, Hj, Gorgievski, M, Hirschel, B, Kaiser, L, Kind, C, Klimkait, T, Lauper, U, Opravil, M, Paccaud, F, Pantaleo, G, Perrin, L, Piffaretti, Jc, Rickenbach, M, Rudin, C, Schupbach, J, Speck, R, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Yerly, S, de Wolf, F, van Sighem, Ai, van Valkengoed, I, Gras, L, Bronsveld, W, Prins, Jm, Bos, Jc, Schattenkerk, Jkme, Godfried, Mh, Lange, Jma, Lowe, Sh, van der Meer, Jtm, Nellen, Fjb, Pogany, K, van der Poll, T, Ruys, Ta, Sankatsing, S, van der Valk, M, van Vonderen, Mga, Wit, Fwmn, van Eeden, A, ten Veen, Jh, van Dam, P, Hillebrand Haverkort, Me, Brinkman, K, Frissen, Phj, Weigel, Hm, Mulder, Jw, van Gorp, Ecm, Meenhorst, Pl, Mairuhu, Ata, Veenstra, J, Danner, Sa, Van Agtmael, Ma, Claessen, Fap, Geerlings, Se, Perenboom, Rm, Richter, C, van der Berg, J, van Leusen, R, Vriesendorp, R, Jeurissen, Fjf, Kauffmann, Rh, Koger, Elw, Bravenboer, B, ten Napel, Chh, Mudrikova, T, Sprenger, Hg, Miesen, Wmaj, ten Kate, Rw, van Houte, Dpf, Leemhuis, Mp, Pole, M, Kroon, Fp, Schippers, Ef, Schreij, G, van de Geest, S, Verbon, A, Koopmans, Pp, Telgt, M, van der Ven, Ajam, van der Ende, Me, Gyssens, Ic, de Marie, S, Nouwen, Jl, Juttmann, Jr, Schneider, Mme, Bonten, Mjm, Borleffs, Jcc, Hoepelman, Im, Jaspers, Cajj, Schouten, I, Schurink, Cam, Blok, Wl, Groenveld, Php, Jurriaans, S, Back, Nkt, Cuijpers, T, Rietra, Pjgm, Roozendaal, Kj, Pauw, W, van Zanten, Ap, Smits, Phm, von Blomberg, Bme, Savelkoul, P, Zaaijer, H, Swanink, C, Franck, Pfh, Lampe, A, Jansen, Cl, Hendriks, R, Schirm, J, Benne, D, Veenendaal, D, Storm, H, van Zeijl, Jh, Kroes, Acm, Claas, Hcj, Bruggeman, Camva, Goossens, Vj, Galama, Jmd, Poort, Yagm, Niesters, Mg, Osterhaus, Adme, Schutten, M, Buiting, Agm, Swaans, Cam, Boucher, Cab, Schuurman, R, Boel, E, Jansz, Af, Veldkamp, A, Beijnen, Jh, Crommentuyn, Kml, 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Subjects
Male, HAART, Human immunodeficiency virus (HIV), CD4 cell count, HIV Infections, CLINICAL PROGRESSION, medicine.disease_cause, THERAPY, HAART REGIMEN, Cohort Studies, Risk Factors, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Cohort Studies, Female, Follow-Up Studies, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Male, Middle Aged, Proportional Hazards Models, Reverse Transcriptase Inhibitors, Risk Factors, Treatment Failure, Viral Load, Medicine, Treatment Failure, Mortality rate, Medicine (all), INHIBITOR, General Medicine, Middle Aged, HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1), BLIND CONTROLLED-TRIAL, medicine.anatomical_structure, Anti-Retroviral Agents, Cohort, HUMAN-IMMUNODEFICIENCY-VIRUS, Reverse Transcriptase Inhibitors, Female, Off Treatment, Viral load, Cohort study, Adult, medicine.medical_specialty, Settore MED/17 - Malattie Infettive, T cell, Internal medicine, Humans, COHORT, Proportional Hazards Models, business.industry, Proportional hazards model, DISEASE PROGRESSION, HIV Protease Inhibitors, HIV-INFECTED INDIVIDUALS, CD4 Lymphocyte Count, VIRAL LOAD, Immunology, HIV-1, business, Follow-Up Studies
Abstract

Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure.Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models.Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% Cl 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per muL versus above 200 cells per muL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1.5 log(10) copies per mL below off-treatment values.Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per muL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1.5 log(10) copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.

Published
2004

9. Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study.

Author

Vasylyev M, Wit FWNM, Jordans CCE, Soetekouw R, van Lelyveld SFL, Kootstra GJ, Delsing CE, Ammerlaan HSM, van Kasteren MEE, Brouwer AE, Leyten EMS, Claassen MAA, Hassing RJ, den Hollander JG, van den Berge M, Roukens AHE, Bierman WFW, Groeneveld PHP, Lowe SH, van Welzen BJ, Richel O, Nellen JF, van den Berk GEL, van der Valk M, Rijnders BJA, and Rokx C

Abstract

Background: Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use., Methods: Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4 + T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin., Results: The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: -3.78% [95% confidence interval {CI}, -7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, -.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued., Conclusions: In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice., Clinical Trials Registration: NCT04707326., Competing Interests: Potential conflicts of interest. F. W. N. M. W. reports consulting fees from ViiV Healthcare. C. R. reports research grants, travel reimbursement, and compensation for participation in scientific boards from ViiV Healthcare and Gilead Sciences. B. J. A. R. reports consulting fees from ViiV Healthcare, Gilead Sciences, and MSD and compensation for educational activities from ViiV Healthcare. M. v. d. V. reports research grants and consulting fees from Gilead Sciences, ViiV Healthcare, and MSD, all paid to his institution. C. C. E. J. reports travel reimbursement from Gilead Sciences and compensation for presentation from ViiV Healthcare. S. v. L. reports a research grant from Pfizer outside the context of this study. J. G. d. H. reports compensation for participation in scientific boards from ViiV Healthcare, Gilead Sciences, Moderna, and GSK. B. J. v. W. reports a research grant from Gilead Sciences, consulting fees from ViiV Healthcare and Gilead Sciences, compensation for participation on a data and safety monitoring board from ViiV Healthcare and Gilead Sciences, and payment for lectures from Gilead Sciences. J. F. N. reports compensation for educational activities and participation in scientific advisory boards from Gilead Sciences, ViiV Healthcare, and MSD, all paid to her institution. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Published
2024
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10. Correction: Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

Author

Hensley KS, Jongkees MJ, Geers D, GeurtsvanKessel CH, Mueller YM, Dalm VASH, Papageorgiou G, Steggink H, Gorska A, Bogers S, den Hollander JG, Bierman WFW, Gelinck LBS, Schippers EF, Ammerlaan HSM, van der Valk M, van Vonderen MGA, Delsing CE, Gisolf EH, Bruns AHW, Lauw FN, Berrevoets MAH, Sigaloff KCE, Soetekouw R, Branger J, de Mast Q, Lammers AJJ, Lowe SH, de Vries RD, Katsikis PD, Rijnders BJA, Brinkman K, Roukens AHE, and Rokx C

Abstract

[This corrects the article DOI: 10.1371/journal.pmed.1003979.]., (Copyright: © 2023 Hensley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2023
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11. Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

Author

Hensley KS, Jongkees MJ, Geers D, GeurtsvanKessel CH, Mueller YM, Dalm VASH, Papageorgiou G, Steggink H, Gorska A, Bogers S, den Hollander JG, Bierman WFW, Gelinck LBS, Schippers EF, Ammerlaan HSM, van der Valk M, van Vonderen MGA, Delsing CE, Gisolf EH, Bruns AHW, Lauw FN, Berrevoets MAH, Sigaloff KCE, Soetekouw R, Branger J, de Mast Q, Lammers AJJ, Lowe SH, de Vries RD, Katsikis PD, Rijnders BJA, Brinkman K, Roukens AHE, and Rokx C

Subjects
Adult, Female, Humans, Male, Middle Aged, Ad26COVS1, Antibodies, Viral, BNT162 Vaccine, Immunogenicity, Vaccine, Immunoglobulin G, Netherlands epidemiology, Prospective Studies, RNA, Messenger, SARS-CoV-2, mRNA Vaccines, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 Vaccines immunology, HIV Infections immunology
Abstract

Background: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH., Methods and Findings: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/μL (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508-0.725, p < 0.001). All controls receiving an mRNA vaccine had an adequate response, defined as >300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250-500 cells/μL (2.845, 95% CI 1.876-4.314, p < 0.001) or >500 cells/μL (2.936, 95% CI 1.961-4.394, p < 0.001), whilst a viral load > 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-γ, CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients., Conclusions: After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required., Trial Registration: The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: All authors have completed the ICMJE disclosure form and declare no competing interests exist directly related to the submitted work Conflicts of interest outside the submitted work CR has received research grants from ViiV, Gilead, ZonMW, AIDSfonds, Erasmus MC, and Health~Holland and honorariums for advisory boards from Gilead and ViiV; WFWB declares reimbursement for participation of patient in trial by GSK to institution. DG and RDdV are supported by the Health~Holland grant EMCLHS20017 co-funded by the PPP Allowance made available by the Health~Holland, Top Sector Life Sciences & Health, to stimulate public–private partnerships. RDdV is listed as inventor of the fusion inhibitory lipopeptide [SARSHRC-PEG4]2-chol on a provisional patent application. VASHD has received research grants from ZonMw, Horizon 2020 – Marie Curie-Sklodowska, Takeda and payments for lectures and advisory boards from Takeda, CSL Behring, Pharming and GSK. KCES received honorariums for advisory boards from Gilead and ViiV. BJAR declares research grants from Gilead and MSD and honorary for advisory boards for Astra Zeneca, Roche, Gilead, F2G all outside the context of this work. RvM received consultancies fees paid to their institution from ViiV; Gilead; MSD, received research grants paid to their institution from ViiV; Gilead All other authors declare hat no competing interests exist.

Published
2022
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12. Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy.

Author

Wijting IEA, Wit FWNM, Rokx C, Leyten EMS, Lowe SH, Brinkman K, Bierman WFW, van Kasteren MEE, Postma AM, Bloemen VCM, Bouchtoubi G, Hoepelman AIM, van der Ende ME, Reiss P, and Rijnders BJA

Abstract

Background: Integrase inhibitors (INI) induce a rapid decline of HIV-RNA in plasma and CD4 + T-cell recovery in blood. Both characteristics are also associated with immune reconstitution inflammatory syndrome (IRIS). Whether the use of INI-containing combination antiretroviral therapy (cART) increases the risk of IRIS is being questioned., Methods: Study within the Dutch ATHENA HIV observational cohort. HIV-1 infected late presenters initiating cART after March 2009 were included if they had <200 CD4 + T-cells per μL and were diagnosed with an opportunistic infection. IRIS was defined either according to the criteria by French et al. (IRIS FRENCH ) or by a clinical IRIS diagnosis of the physician (IRIS CLINICAL ). The primary outcomes were the association between INI and the occurrence of IRIS FRENCH and IRIS FRENCH+CLINICAL in multivariable logistic regression., Findings: 672 patients with a median CD4 + T-cell count of 35 cells per μL were included. Treatment with INI was independently associated with IRIS FRENCH as well as IRIS FRENCH+CLINICAL (OR 2·43, 95%CI:1·45-4·07, and OR 2·17, 95%CI:1·45-3·25). When investigating INI separately, raltegravir (RAL) remained significantly associated with IRIS FRENCH (OR 4·04 (95%CI:1·99-8·19) as well as IRIS FRENCH+CLINICAL (OR 3·07, 95%CI:1·66-5·69), while dolutegravir (DTG) became associated with IRIS FRENCH+CLINICAL after it replaced RAL as preferred INI in the cohort after 2015 (OR 4·08, 95%CI:0·99-16·82, p =0·052). Too few patients used elvitegravir to draw meaningful conclusions. Steroid initiation for IRIS was more likely in those who initiated INI versus in those who did not, but no increased hospital (re)admission or mortality rates were observed., Interpretation: In HIV late presenters from a resource rich setting, INI based treatment initiation increased the risk of IRIS. This was observed for RAL and DTG when being initiated as preferential INI in the presence of specific AIDS-conditions, indicative of channeling bias. Although we controlled for all relevant measured confounders, we cannot exclude that the observed association is partially explained by residual confounding. INI use was not associated with mortality nor hospitalization. Therefore, our observation is no reason to avoid INI in late presenters., Funding: The ATHENA database is maintained by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment., (© 2019 Published by Elsevier Ltd.)

Published
2019
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13. Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy.

Author

Peltenburg NC, Schoeman JC, Hou J, Mora F, Harms AC, Lowe SH, Bierau J, Bakker JA, Verbon A, Hankemeier T, and Boonstra A

Subjects
Adult, Biogenic Amines immunology, Biogenic Amines metabolism, Biomarkers blood, Biomarkers metabolism, Cohort Studies, Female, HIV Infections metabolism, HIV Infections virology, HIV-1 immunology, HIV-1 physiology, Host-Pathogen Interactions drug effects, Host-Pathogen Interactions immunology, Humans, Lipids analysis, Lipids immunology, Lymphocyte Count, Male, Middle Aged, Anti-Retroviral Agents therapeutic use, Antiretroviral Therapy, Highly Active methods, HIV Infections drug therapy, HIV-1 drug effects, Metabolomics methods
Abstract

The HIV-human metabolic relationship is a complex interaction convoluted even more by antiretroviral therapy (cART) and comorbidities. The ability of cART to undo the HIV induced metabolic dysregulation is unclear and under-investigated. Using targeted metabolomics and multiplex immune biomarker analysis, we characterized plasma samples obtained from 18 untreated HIV-1-infected adult patients and compared these to a non-HIV infected (n = 23) control population. The biogenic amine perturbations during an untreated HIV infection implicated altered tryptophan- nitrogen- and muscle metabolism. Furthermore, the lipid profiles of untreated patients were also significantly altered compared to controls. In untreated HIV infection, the sphingomyelins and phospholipids correlated negatively to markers of infection IP-10 and sIL-2R whereas a strong association was found between triglycerides and MCP-1. In a second cohort, we characterized plasma samples obtained from 28 HIV-1-infected adult patients before and 12 months after the start of cART, to investigate the immune-metabolic changes associated with cART. The identified altered immune-metabolic pathways of an untreated HIV infection showed minimal change after 12 months of cART. In conclusion, 12 months of cART impacts only mildly on the metabolic dysregulation underlying an untreated HIV infection and provide insights into the comorbidities present in virally suppressed HIV patients.

Published
2018
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14. Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV.

Author

Peltenburg NC, Bierau J, Bakker JA, Schippers JA, Lowe SH, Paulussen ADC, van den Bosch BJC, Leers MPG, Hansen BE, and Verbon A

Subjects
Adult, Aged, Aged, 80 and over, Anti-HIV Agents administration & dosage, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Young Adult, Inosine Triphosphatase, Anti-HIV Agents therapeutic use, Biomarkers blood, Erythrocytes enzymology, HIV Infections drug therapy, Pyrophosphatases blood
Abstract

The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5'-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity ≥4 mmol IMP/mmol Hb/hour was considered as normal. ITPA genotype was determined by testing two ITPA polymorphisms: c.94C>A (p.Pro32Thr, rs1127354) and c.124+21A>C (rs7270101). Logistic regression analysis determined odds ratios for developing AEs. In tenofovir-containing regimens decreased ITPase activity was associated with less AEs (p = 0.01) and longer regimen duration (p = 0.001). In contrast, in abacavir-containing regimens decreased ITPase activity was associated with more AEs (crude p = 0.02) and increased switching of medication due to AEs (p = 0.03). ITPA genotype wt/wt was significantly associated with an increase in the occurrence of AEs in tenofovir-containing regimens. Decreased ITPase activity seems to be protective against occurrence of AEs in tenofovir-containing cART, while it is associated with an increase in AEs in abacavir-containing regimens.

Published
2018
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15. Inosine Triphosphate Pyrophosphohydrolase Expression: Decreased in Leukocytes of HIV-Infected Patients Using Combination Antiretroviral Therapy.

Author

Peltenburg NC, Leers MP, Bakker JA, Lowe SH, Vroemen WH, Paulussen AD, van den Bosch BJ, Bierau J, and Verbon A

Subjects
Adult, Aged, Case-Control Studies, Drug Therapy, Combination, Female, Genotype, HIV Infections metabolism, Humans, Male, Middle Aged, Pyrophosphatases genetics, Inosine Triphosphatase, Anti-HIV Agents therapeutic use, Gene Expression Regulation, Enzymologic drug effects, HIV Infections drug therapy, Leukocytes enzymology, Pyrophosphatases metabolism
Abstract

Objective: In HIV-infected patients, the enzyme Inosine triphosphate pyrophosphohydrolase (ITPase), involved in purine nucleotide homeostasis, was found to be decreased in erythrocytes. Since purine analogues are pivotal in the HIV treatment, a better understanding of ITPase expression in CD4 lymphocytes may lead to better understanding of nucleotide metabolism and (adverse) effects., Design: Cross-sectional, cohort, observational study., Methods: HIV-infected and control patients above 18 years were included. All DNA samples were genotyped for the 2 functional ITPA SNPs; c.94C>A (rs1127354) and g.IVS+21A>C (rs7270101). ITPase expression was determined by flow cytometry in all leukocyte subsets., Results: Fifty-nine HIV-infected patients and 50 controls were included. Leukocyte subtype distribution showed no difference in monocytes and granulocytes, but lymphocytes were higher in HIV-infected patients (P < 0.001). ITPase expression was highest in activated monocytes and lowest in lymphocytes. In HIV-infected patients, the percentage of ITPase positive cells was less in all leukocyte and lymphocyte subsets compared with controls (P < 0.01). In HIV-infected patients, 97.4% of CD4 lymphocytes were ITPase positive versus 99.9% in controls (P = 0.002) and 85.9% versus 99.6% of CD8 lymphocytes (P < 0.0001), respectively. Stratification according to genotype revealed no significant differences in ITPase expression in leukocytes in HIV-infected and control patients., Conclusions: HIV-infection seems to be interfering with the nucleotide metabolism in leukocytes, including CD4 lymphocytes, by decreasing ITPase expression, independently of ITPA genotype. Given that active metabolites of purine-analogue reverse transcriptase inhibitors are potential substrates for ITPase, these results warrant further research towards effectiveness and adverse events of purine analogues and ITPase activity.

Published
2016
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16. Improving sexual health for HIV patients by providing a combination of integrated public health and hospital care services; a one-group pre- and post test intervention comparison.

Author

Dukers-Muijrers NH, Somers C, Hoebe CJ, Lowe SH, Niekamp AM, Oude Lashof A, Bruggeman CA, and Vrijhoef HJ

Subjects
Delivery of Health Care, Integrated statistics & numerical data, Female, Heterosexuality, Homosexuality, Male, Humans, Male, Mass Screening, Needs Assessment, Netherlands, Patient Satisfaction statistics & numerical data, Treatment Outcome, Counseling, Delivery of Health Care, Integrated organization & administration, HIV Infections therapy, Outpatient Clinics, Hospital, Public Health Practice, Quality Assurance, Health Care, Sexually Transmitted Diseases diagnosis
Abstract

Background: Hospital HIV care and public sexual health care (a Sexual Health Care Centre) services were integrated to provide sexual health counselling and sexually transmitted infections (STIs) testing and treatment (sexual health care) to larger numbers of HIV patients. Services, need and usage were assessed using a patient perspective, which is a key factor for the success of service integration., Methods: The study design was a one-group pre-test and post-test comparison of 447 HIV-infected heterosexual individuals and men who have sex with men (MSM) attending a hospital-based HIV centre serving the southern region of the Netherlands. The intervention offered comprehensive sexual health care using an integrated care approach. The main outcomes were intervention uptake, patients' pre-test care needs (n=254), and quality rating., Results: Pre intervention, 43% of the patients wanted to discuss sexual health (51% MSM; 30% heterosexuals). Of these patients, 12% to 35% reported regular coverage, and up to 25% never discussed sexual health topics at their HIV care visits. Of the patients, 24% used our intervention. Usage was higher among patients who previously expressed a need to discuss sexual health. Most patients who used the integrated services were new users of public health services. STIs were detected in 13% of MSM and in none of the heterosexuals. The quality of care was rated good., Conclusions: The HIV patients in our study generally considered sexual health important, but the regular counselling and testing at the HIV care visit was insufficient. The integration of public health and hospital services benefited both care sectors and their patients by addressing sexual health questions, detecting STIs, and conducting partner notification. Successful sexual health care uptake requires increased awareness among patients about their care options as well as a cultural shift among care providers.

Published
2012
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17. Erythrocyte inosine triphosphatase activity is decreased in HIV-seropositive individuals.

Author

Bierau J, Bakker JA, Schippers JA, Grashorn JA, Lindhout M, Lowe SH, Paulussen AD, and Verbon A

Subjects
Alleles, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, Biocatalysis drug effects, Cell Line, Tumor, Cohort Studies, Female, Gene Frequency, Genotype, HIV Seropositivity drug therapy, HIV Seropositivity genetics, Humans, Kinetics, Male, Middle Aged, Nucleosides chemistry, Nucleosides therapeutic use, Polymorphism, Single Nucleotide, Pyrophosphatases genetics, White People genetics, White People statistics & numerical data, Erythrocytes enzymology, Genetic Association Studies, HIV Seropositivity enzymology, Pyrophosphatases metabolism
Abstract

Background: Inosine triphosphatase (ITPase) is encoded by the polymorphic gene ITPA and maintains low intracellular levels of the inosine nucleotides ITP and dITP. The most frequently reported polymorphisms are ITPA c.94C>A (rs 1127354) and ITPA c. 124+21 A>C (rs7270101). Some nucleoside-analogues used in the treatment of HIV-seropositive (HIV+) patients are potential substrates for ITPase. Therefore, the frequency of ITPA SNPs and ITPase activity were studied in a population of HIV+-patients., Methods: The study population consisted of 222 patients, predominantly Caucasian males, >95% using HAART. Erythrocyte ITPase activity was determined by measuring the formation of IMP from ITP. ITPA genotype was determined by sequencing genomic DNA. Distribution of ITPase activity, genotype-phenotype correlation and allele frequencies were compared to 198 control subjects. The effect of nucleoside analogues on ITPase activity was studied using lymphoblastic T-cell cultures and human recombinant ITPase. Enzyme kinetic experiments were performed on erythrocyte ITPase from HIV+ patients and controls., Results: No difference was observed in the allele frequencies between the HIV+-cohort (± HAART) and the control population. HIV+ carriers of the wild type and ITPA c.94C>A had significantly lower ITPase activities than control subjects with the same genotype (p<0.005). This was not observed in ITPA c. 124+21 A>C carriers. Nucleoside analogues did not affect ITPase activity in cell culture and human recombinant ITPase., Conclusion: ITPA population genetics were identical in HIV+ and control populations. However, the majority of HIV+-patients had decreased erythrocyte ITPase activity compared to controls, probably due to decreased amounts of ITPase protein. It seems unlikely that ITPase activity is decreased due to nucleoside analogues (HAART). Long-term effects of HIV-infection altering ITPase protein expression or stability may explain the phenomenon observed.

Published
2012
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18. Semen parameters of a semen donor before and after infection with human immunodeficiency virus type 1: case report.

Author

van Leeuwen E, Cornelissen M, de Vries JW, Lowe SH, Jurriaans S, Repping S, and van der Veen F

Subjects
Adult, Humans, Male, Middle Aged, Semen Preservation, Sperm Motility, Spermatozoa virology, HIV Infections pathology, HIV-1, Semen physiology, Semen virology, Spermatozoa pathology, Tissue Donors
Abstract

Semen samples from a donor who seroconverted for human immunodeficiency virus type 1 (HIV-1) during the period that he was donating at our clinic were stored before and after infection. Semen analysis was done on all of these samples before cryopreservation. Retrospectively, both qualitative and quantitative HIV-1 testing was performed on the cryopreserved semen samples to determine the time of primary HIV-1 infection. After HIV-1 infection, semen volume, sperm motility and the percentage of spermatozoa with normal morphology were reduced compared with the same parameters before HIV-1 infection. HIV-1 RNA was intermittently detectable in semen. HIV-1 infection led to a reduction in semen volume, sperm motility and normal sperm morphology in this donor. However, the clinical significance of these findings is unclear. A longitudinal cohort study on the effects of HIV-1 infection on semen quality is necessary to confirm these findings.

Published
2004
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19. Antiretroviral therapy in previously untreated adults infected with the human immunodeficiency virus type I: established and potential determinants of virological outcome.

Author

Lowe SH, Prins JM, and Lange JM

Subjects
HIV Infections virology, Humans, Viral Load, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, HIV-1
Abstract

The aim of highly active antiretroviral therapy (HAART) for patients chronically infected with the human immunodeficiency virus type I is to achieve maximal and durable viral suppression. Maintaining the blood plasma HIV-I-RNA concentration (pVL) <50 copies/ml is currently considered appropriate for this goal. With the current treatment options, the percentage of previously untreated patients who achieve a pVL <50 copies/ml after one year of initial HAART is about 70%. Characteristics of the host, virus, drugs and the treatment team have been associated with the virological response to initial HAART. Adjusting the initial HAART regimen and patient management to a risk profile based on these factors is possibly helpful in improving the virological response to HAART. Adherence to a potent and well-tolerated HAART regimen is likely to be the most relevant factor for virological success. The additive value of the other factors needs to be clarified.

Published
2004

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