Author: "Günthard, Huldrych" / Publisher: oxford university press - Searchworks@Jio Institute Digital Library Search Results

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246 results on '"Günthard, Huldrych"'

1. Genetic diversity from proviral DNA as a proxy for time since HIV-1 infection

Author: Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Frischknecht, Paul, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Schenkel, Corinne D, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Leeman, Christine, Notter, Julia, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Stöckle, Marcel; https://orcid.org/0000-0002-0088-5078, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Frischknecht, Paul, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Schenkel, Corinne D, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Leeman, Christine, Notter, Julia, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Stöckle, Marcel; https://orcid.org/0000-0002-0088-5078, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, and Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348
Abstract: HIV-1 RNA genetic diversity predicts time since infection which is important for clinical care and research. It's unclear, however, whether proviral DNA genetic diversity sampled under suppressive antiretroviral therapy can be used for this purpose. We tested whether proviral genetic diversity from NGS sequences predicts time since infection and recency in 221 people with HIV-1 with known infection time. Proviral diversity was significantly associated with time since infection (p<5*10-07, R2 up to 25%) and predictive of treatment initiation during recent infection (AUC-ROC up to 0.85). This shows the utility of proviral genetic diversity as a proxy for time since infection.
Published: 2024

2. Deciphering factors linked with reduced SARS-CoV-2 susceptibility in the Swiss HIV Cohort Study

Author: Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Epp, Selina, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Battegay, Manuel; https://orcid.org/0000-0002-6638-3679, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Notter, Julia, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fux, Christoph A, Leuzinger, Karoline; https://orcid.org/0000-0002-5654-9356, Perreau, Matthieu, Ramette, Alban; https://orcid.org/0000-0002-3437-4639, Gottschalk, Jochen, Schindler, Eméry, Wepf, Alexander, Marconato, Maddalena, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Frey, Beat M; https://orcid.org/0000-0002-2514-8621, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Swiss HIV Cohort Study, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Schwarzmüller, Magdalena; https://orcid.org/0000-0001-8384-2518, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Epp, Selina, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Battegay, Manuel; https://orcid.org/0000-0002-6638-3679, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Notter, Julia, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fux, Christoph A, Leuzinger, Karoline; https://orcid.org/0000-0002-5654-9356, Perreau, Matthieu, Ramette, Alban; https://orcid.org/0000-0002-3437-4639, Gottschalk, Jochen, Schindler, Eméry, Wepf, Alexander, Marconato, Maddalena, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Frey, Beat M; https://orcid.org/0000-0002-2514-8621, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, and Swiss HIV Cohort Study
Abstract: BACKGROUND Factors influencing susceptibility to SARS-CoV-2 remain to be resolved. Using data of the Swiss HIV Cohort Study (SHCS) on 6,270 people with HIV (PWH) and serologic assessment for SARS-CoV-2 and circulating-human-coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection. METHODS We analyzed SARS-CoV-2 PCR-tests, COVID-19 related hospitalizations, and deaths reported to the SHCS between January 1, 2020 and December 31, 2021. Antibodies to SARS-CoV-2 and HCoVs were determined in pre-pandemic (2019) and pandemic (2020) bio-banked plasma and compared to HIV-negative individuals. We applied logistic regression, conditional logistic regression, and Bayesian multivariate regression to identify determinants of SARS-CoV-2 infection and Ab responses to SARS-CoV-2 in PWH. RESULTS No HIV-1-related factors were associated with SARS-CoV-2 acquisition. High pre-pandemic HCoV antibodies were associated with a lower risk of subsequent SARS-CoV-2 infection and with higher SARS-CoV-2 antibody responses upon infection. We observed a robust protective effect of smoking on SARS-CoV-2-infection risk (aOR= 0.46 [0.38,0.56], p=2.6*10-14), which occurred even in previous smokers, and was highest for heavy smokers. CONCLUSIONS Our findings of two independent protective factors, smoking and HCoV antibodies, both affecting the respiratory environment, underscore the importance of the local immune milieu in regulating susceptibility to SARS-CoV-2.
Published: 2024

3. Circulating HBV RNA and Hepatitis B Core–Related Antigen Trajectories in Persons With HIV/HBV Coinfection and Hepatitis B Surface Antigen Loss During Tenofovir Therapy

Author: Begré, Lorin; https://orcid.org/0000-0003-1015-8947, Boyd, Anders; https://orcid.org/0000-0001-9512-8928, Plissonnier, Marie-Laure; https://orcid.org/0000-0003-4879-4586, Testoni, Barbara; https://orcid.org/0000-0001-5588-5465, Salazar-Vizcaya, Luisa; https://orcid.org/0000-0003-0527-0141, Suter-Riniker, Franziska; https://orcid.org/0000-0001-8568-578X, Scholtès, Caroline; https://orcid.org/0000-0003-0691-8480, Béguelin, Charles; https://orcid.org/0000-0001-9346-5146, Rockstroh, Jürgen K; https://orcid.org/0000-0003-2858-3888, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Schmid, Patrick; https://orcid.org/0000-0003-1978-5082, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Levrero, Massimo; https://orcid.org/0000-0002-4978-0875, Wandeler, Gilles; https://orcid.org/0000-0002-5278-8763, Zoulim, Fabien; https://orcid.org/0000-0002-2245-0083, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Swiss HIV Cohort Study, Begré, Lorin; https://orcid.org/0000-0003-1015-8947, Boyd, Anders; https://orcid.org/0000-0001-9512-8928, Plissonnier, Marie-Laure; https://orcid.org/0000-0003-4879-4586, Testoni, Barbara; https://orcid.org/0000-0001-5588-5465, Salazar-Vizcaya, Luisa; https://orcid.org/0000-0003-0527-0141, Suter-Riniker, Franziska; https://orcid.org/0000-0001-8568-578X, Scholtès, Caroline; https://orcid.org/0000-0003-0691-8480, Béguelin, Charles; https://orcid.org/0000-0001-9346-5146, Rockstroh, Jürgen K; https://orcid.org/0000-0003-2858-3888, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Schmid, Patrick; https://orcid.org/0000-0003-1978-5082, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Levrero, Massimo; https://orcid.org/0000-0002-4978-0875, Wandeler, Gilles; https://orcid.org/0000-0002-5278-8763, Zoulim, Fabien; https://orcid.org/0000-0002-2245-0083, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, and Swiss HIV Cohort Study
Abstract: Background We evaluated long-term trajectories of circulating hepatitis B virus (HBV) RNA and hepatitis B core–related antigen (HBcrAg) in persons with and without hepatitis B surface antigen (HBsAg) loss during tenofovir therapy in the Swiss HIV Cohort Study. Methods We included 29 persons with HIV with HBsAg loss and 29 matched persons with HIV without HBsAg loss. We compared HBV RNA and HBcrAg decline and assessed the cumulative proportions with undetectable HBV RNA and HBcrAg levels during tenofovir therapy using Kaplan-Meier estimates. Results HBsAg loss occurred after a median of 4 years (IQR, 1–8). All participants with HBsAg loss achieved suppressed HBV DNA and undetectable HBV RNA preceding undetectable quantitative HBsAg levels, whereas 79% achieved negative HBcrAg. In comparison, 79% of participants without HBsAg loss achieved undetectable HBV-RNA and 48% negative HBcrAg. After 2 years of tenofovir therapy, an HBV RNA decline ≥1 log10 copies/mL had 100% sensitivity and 36.4% specificity for HBsAg loss, whereas an HBcrAg decline ≥1 log10 U/mL had 91.0% sensitivity and 64.5% specificity. Conclusions HBV RNA suppression preceded undetectable quantitative HBsAg levels and had high sensitivity but low specificity for HBsAg loss during tenofovir therapy in persons with HIV. HBcrAg remained detectable in approximately 20% of persons with HBsAg loss and 50% of persons without HBsAg loss.
Published: 2024

4. Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration

Author: Tusch, E, Ryom, L, Pelchen-Matthews, A, Mocroft, A, Elbirt, D, Oprea, C, Günthard, H, Staehelin, C, Zangerle, R, Suarez, I, Vehreschild, J, Wit, F, Menozzi, M, d'Arminio Monforte, A, Spagnuolo, V, Pradier, C, Carlander, C, Suanzes, P, Wasmuth, J, Carr, A, Petoumenos, K, Borgans, F, Bonnet, F, De Wit, S, El-Sadr, W, Neesgaard, B, Jaschinski, N, Greenberg, L, Hosein, S, Gallant, J, Vannappagari, V, Young, L, Sabin, C, Lundgren, J, Peters, L, Reekie, J, Calvo, G, Dabis, F, Kirk, O, Law, M, Monforte, A, Morfeldt, L, Reiss, P, Weber, R, Lind-Thomsen, A, Brandt, R, Hillebreght, M, Zaheri, S, Scherrer, A, Schöni-Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Marec, F, Boerg, E, Thulin, E, Sundström, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Dollet, K, Mateu, S, Torres, F, Blance, A, Huang, R, Puhr, R, Laut, K, Kristensen, D, Phillips, A, Kamara, D, Smith, C, Hatleberg, C, Raben, D, Matthews, C, Bojesen, A, Grevsen, A, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Smit, C, Ross, M, Fux, C, Morlat, P, Friis-Møller, N, Kowalska, J, Bohlius, J, Bower, M, Fätkenheuer, G, Grulich, A, Sjøl, A, Meidahl, P, Iversen, J, Reiss, C, Hillebregt, M, Prins, J, Kuijpers, T, Scherpbier, H, van der Meer, J, Godfried, M, van der Poll, T, Nellen, F, Geerlings, S, van Vugt, M, Pajkrt, D, Bos, J, Wiersinga, W, van der Valk, M, Goorhuis, A, Hovius, J, van Eden, J, Henderiks, A, van Hes, A, Mutschelknauss, M, Nobel, H, Pijnappel, F, Jurriaans, S, Back, N, Zaaijer, H, Berkhout, B, Cornelissen, M, Schinkel, C, Thomas, X, Ziekenhuis, A, van den Berge, M, Stegeman, A, Baas, S, de Looff, L, Versteeg, D, Ziekenhuis, C, Pronk, M, Ammerlaan, H, De Munnik, E, Jansz, A, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, van der Plas, A, Weijsenfeld, A, van der Ende, M, De Vries-Sluijs, T, van Gorp, E, Schurink, C, Nouwen, J, Verbon, A, Rijnders, B, Bax, H, van der Feltz, M, Bassant, N, van Beek, J, Vriesde, M, van Zonneveld, L, de Oude-Lubbers, A, van den Berg-Cameron, H, Bruinsma-Broekman, F, de Groot, J, de Man, M, Boucher, C, Koopmans, M, van Kampen, J, Pas, S, Mc–sophia, E, Driessen, G, van Rossum, A, van der Knaap, L, Visser, E, Branger, J, Rijkeboer-Mes, A, de Ven, C, Ziekenhuis, H, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, Franck, P, van Eeden, A, Brokking, W, Groot, M, Elsenburg, L, Damen, M, Kwa, I, Groeneveld, P, Bouwhuis, J, van den Berg, J, van Hulzen, A, van der Bliek, G, Bor, P, Bloembergen, P, Wolfhagen, M, Ruijs, G, Kroon, F, de Boer, M, Bauer, M, Jolink, H, Vollaard, A, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander, J, Pogany, K, Roukens, A, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, S, Lashof, A, Posthouwer, D, Ackens, R, Schippers, J, Vergoossen, R, Weijenberg-Maes, B, van Loo, I, Havenith, T, Leyten, E, Gelinck, L, van Hartingsveld, A, Meerkerk, C, Wildenbeest, G, Mutsaers, J, Jansen, C, Mulder, J, Vrouenraets, S, Lauw, F, van Broekhuizen, M, Paap, H, Vlasblom, D, Smits, P, Zuiderzee, M, Weijer, S, El Moussaoui, R, Bosma, A, van Vonderen, M, van Houte, D, Kampschreur, L, Dijkstra, K, Faber, S, Weel, J, Kootstra, G, Delsing, C, van der Burg-van de Plas, M, Heins, H, Lucas, E, Kortmann, W, van Twillert, G, Stuart, J, Diederen, B, Pronk, D, van Truijen-Oud, F, van der Reijden, W, Jansen, R, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, van der Meché, I, Spelbrink, M, Sulman, H, Toonen, A, Wijnands, S, Kwa, D, Witte, E, Koopmans, P, Keuter, M, van der Ven, A, ter Hofstede, H, Dofferhoff, A, van Crevel, R, Albers, M, Bosch, M, Grintjes-Huisman, K, Zomer, B, Stelma, F, Rahamat-Langendoen, J, Burger, D, Richter, C, Gisolf, E, Hassing, R, 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, B, Veenendaal, D, Verhagen, D, van Wijk, M, Ziekenhuis, S, van Kasteren, M, Brouwer, A, de Wiel, B, Kuipers, M, Santegoets, R, van der Ven, B, Marcelis, J, Buiting, A, Kabel, P, Bierman, W, Scholvinck, H, Wilting, K, Stienstra, Y, Jonge, H, van der Meulen, P, de Weerd, D, Ludwig-Roukema, J, Niesters, H, Riezebos-Brilman, A, van Leer-Buter, C, Knoester, M, Hoepelman, A, Mudrikova, T, Ellerbroek, P, Oosterheert, J, Arends, J, Barth, R, Wassenberg, M, Schadd, E, van Elst-Laurijssen, D, van Oers-Hazelzet, E, Vervoort, S, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Peters, E, van Agtmael, M, Bomers, M, de Vocht, J, Heitmuller, M, Laan, L, Pettersson, A, Vandenbroucke-Grauls, C, Ang, C, Kinderziekenhuis, W, Geelen, S, Wolfs, T, Bont, L, Nauta, N, Bezemer, D, van Sighem, A, Boender, T, de Jong, A, Bergsma, D, Hoekstra, P, de Lang, A, Grivell, S, Jansen, A, Rademaker, M, 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, J, Tchamgoué, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, M, 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, F, De Witte, S, 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, M, Rispal, P, Sorin, L, Valette, C, Viallard, J, Wille, H, Wirth, G, Lafon, M, Trimoulet, P, Bellecave, P, Tumiotto, C, Haramburu, F, Miremeont-Salamé, G, Blaizeau, M, Decoin, M, Hannapier, C, Lenaud, E, Pougetoux, A, Delveaux, S, D’Ivernois, C, Diarra, F, Uwamaliya-Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Law, C, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Cooper, D, O’Sullivan, M, Nolan, D, Guelfi, G, Calvo, C, Domingo, P, Sambeat, M, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, Clumeck, N, Gennotte, A, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, M, Semaille, P, Van Laethem, Y, Neaton, C, Krum, E, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, D, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, L, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Losso, M, Pedersen, C, Ristola, M, Rockstroh, J, Fischer, A, Larsen, J, Podlekareva, D, Cozzi-Lepri, A, Shepherd, L, Schultze, A, Amele, S, Kundro, M, Schmied, B, Wien, P, Vassilenko, A, Mitsura, V, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Møller, N, Ostergaard, L, Wiese, L, Nielsen, L, Zilmer, K, Smidt, J, Siseklinik, N, Aho, I, Viard, J, Duvivier, C, Schmidt, R, Degen, O, Stellbrink, H, Stefan, C, Goethe, J, Bogner, J, Chkhartishvili, N, Gargalianos, P, Xylomenos, G, Armenis, K, Sambatakou, H, Szlávik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Sthoeger, Z, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Annunziata, O, 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, Matulionyte, R, Staub, T, Hemmer, R, 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, Mansinho, K, Maltez, F, Radoi, R, Panteleev, A, Panteleev, O, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Blokhina, I, Novogrod, N, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Miró, J, Moreno, S, Rodriguez, J, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, J, Sonnerborg, A, Brännström, I, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, A, Simons, E, Johnson, M, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Morfeldt, C, Thulin, G, Åkerlund, B, Koppel, K, Karlsson, A, Håkangård, C, Castelli, F, Cauda, R, Perri, G, Iardino, R, Ippolito, G, Marchetti, G, Perno, C, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Caputo, S, Puoti, M, 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A, Mitsura, V, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Møller, N, Ostergaard, L, Wiese, L, Nielsen, L, Zilmer, K, Smidt, J, Siseklinik, N, Aho, I, Viard, J, Duvivier, C, Schmidt, R, Degen, O, Stellbrink, H, Stefan, C, Goethe, J, Bogner, J, Chkhartishvili, N, Gargalianos, P, Xylomenos, G, Armenis, K, Sambatakou, H, Szlávik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Sthoeger, Z, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Annunziata, O, 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, Matulionyte, R, Staub, T, Hemmer, R, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, 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Maddaloni, L, Cattelan, A, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, M, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Sulekova, L, Iaiani, G, Latini, A, Mastrorosa, I, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Del Vecchio, R, Francisci, D, Giuli, C, Caramello, P, Orofino, G, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Central, C, 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, P, Aubert, V, Bernasconi, E, Böni, J, Braun, D, Bucher, H, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Haerry, D, Hasse, B, Hirsch, H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B, Marzolini, C, Metzner, K, Müller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S, Valk, M, Hutchinson, J, Rupasinghe, D, Han, W, Appoyer, H, Vera, J, Broster, B, Barbour, L, Carney, D, Greenland, L, Coughlan, R, Saint-Pierre, C, Stephan, C, Bucht, M, Chokoshvili, O, Borghi, V, Casabona, J, Miro, J, Lampe, F, Burns, F, Chaloner, C, Muccini, C, Lolatto, R, Sönnerborg, A, Nowak, P, Vesterbacka, J, Mattsson, L, Carrick, D, Stigsäter, K, Kusejko, K, Schulze, N, Franke, B, Rooney, J, Mcnicholl, I, Garges, H, Campo, R, Volny-Anne, A, Dedes, N, Williams, E, Bruguera, A, Volny-Anne, R, Mendão, L, Timiryasova, A, Fursa, O, Jakobsen, M, Kraef, C, Gardizi, M, Andersen, K, Kumar, L, Elsing, T, Shahi, S, Valdenmaiier, O, Bansi-Matharu, L, Byonanebye, D, Bannister, W, Roen, A, Null, N, Tusch, Erich, Ryom, Lene, Pelchen-Matthews, Annegret, Mocroft, Amanda, Elbirt, Daniel, Oprea, Cristiana, Günthard, Huldrych F, Staehelin, Cornelia, Zangerle, Robert, Suarez, Isabelle, Vehreschild, Jörg Janne, Wit, Ferdinand, Menozzi, Marianna, d'Arminio Monforte, Antonella, Spagnuolo, Vincenzo, Pradier, Christian, Carlander, Christina, Suanzes, Paula, Wasmuth, Jan-Christian, Carr, Andrew, Petoumenos, Kathy, Borgans, Frauke, Bonnet, Fabrice, De Wit, Stephane, El-Sadr, Wafaa, Neesgaard, Bastian, Jaschinski, Nadine, Greenberg, Lauren, Hosein, Sean R, Gallant, Joel, Vannappagari, Vani, Young, Lital, Sabin, Caroline, Lundgren, Jens, Peters, Lars, Reekie, Joanne, Monforte, A d’Arminio, Brandt, R Salbøl, Wit, F W N M, Marec, F Le, Laut, K Grønborg, Sabin, C A, Phillips, A N, Kamara, D A, Smith, C J, Hatleberg, C I, Brandt, R S, Grevsen, A L, Lundgren, J D, Fux, C A, Monforte, A d'Arminio, Iversen, J S, Reiss, Central P, Prins, J M, Kuijpers, T W, Scherpbier, H J, van der Meer, J T M, Godfried, M H, Nellen, F J B, Geerlings, S E, Bos, J C, Wiersinga, W J, Hovius, J W, van Hes, A M H, Nobel, H E, Pijnappel, F J J, Back, N K T, Zaaijer, H L, Cornelissen, M T E, Schinkel, C J, Thomas, X V, Ziekenhuis, Admiraal De Ruyter, de Looff, L Hage, Ziekenhuis, Catharina, Pronk, M J H, Ammerlaan, H S M, De Munnik, E S, Jansz, A R, Wegdam, M C A, Weijsenfeld, A M, van der Ende, M E, De Vries-Sluijs, T E M S, van Gorp, E C M, Schurink, C A M, Nouwen, J L, Rijnders, B J A, Bax, H I, van Beek, J E A, van Zonneveld, L M, van den Berg-Cameron, H J, Bruinsma-Broekman, F B, de Man, M de Zeeuw, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Pas, S D, MC–Sophia, Erasmus, Driessen, G J A, van Rossum, A M C, van der Knaap, L C, de Ven, C J H M Duijf-van, Ziekenhuis, Haga, Schippers, E F, van IJperen, J M, Franck, P F H, Elsenburg, L J M, Kwa, I S, Groeneveld, P H P, Bouwhuis, J W, van den Berg, J F, van Hulzen, A G W, van der Bliek, G L, Bor, P C J, Wolfhagen, M J H M, Ruijs, G J H M, Kroon, F P, de Boer, M G J, Bauer, M P, Vollaard, A M, Claas, E C J, den Hollander, J G, Smit, J V, Lowe, S H, Lashof, A M L Oude, Ackens, R P, van Loo, I H M, Havenith, T R A, Leyten, E M S, Gelinck, L B S, Wildenbeest, G S, Mutsaers, J A E M, Jansen, C L, Mulder, J W, Vrouenraets, S M E, Lauw, F N, van Broekhuizen, M C, Vlasblom, D J, Smits, P H M, Zuiderzee, M C, Bosma, A S, van Vonderen, M G A, van Houte, D P F, Kampschreur, L M, Kootstra, G J, Delsing, C E, Stuart, J W T Cohen, Diederen, B M W, van Truijen-Oud, F A, van der Reijden, W A, van den Berk, G E L, Blok, W L, Frissen, P H J, Lettinga, K D, Schouten, W E M, Brouwer, C J, Geerders, G F, Kleene, M J, van der Meché, I B, Toonen, A J M, Koopmans, P P, van der Ven, A J A M, ter Hofstede, H J M, Dofferhoff, A S M, Bosch, M E W, Grintjes-Huisman, K J T, Zomer, B J, Stelma, F F, Gisolf, E H, Hassing, R J, van Bentum, P H M, Swanink, C M A, van Lelyveld, S F L, van der Prijt, L M M, Herpers, B L, Verhagen, D W M, Ziekenhuis, St Elisabeth, van Kasteren, M E E, Brouwer, A E, de Wiel, B A F M de Kruijf-van, Santegoets, R M W J, Marcelis, J H, Buiting, A G M, Kabel, P J, Bierman, W F W, Wilting, K R, Jonge, H de Groot-de, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Hoepelman, A I M, Ellerbroek, P M, Oosterheert, J J, Arends, J E, Barth, R E, Wassenberg, M W M, Schadd, E M, van Elst-Laurijssen, D H M, van Oers-Hazelzet, E E B, Wensing, A M J, Peters, E J G, van Agtmael, M A, Laan, L M, Pettersson, A M, Vandenbroucke-Grauls, C M J E, Ang, C W, Kinderziekenhuis, Wilhelmina, Geelen, S P M, Wolfs, T F W, Bont, L J, Bezemer, D O, van Sighem, A I, Boender, T S, Rademaker, M J, Pellegrin, J L, Vareil, M O, Dauchy, F A, Receveur, M C, Vandenhende, M A, Viallard, J F, Lafon, Me, Blaizeau, M J, Boerg, Eloïse, Law, Central M, Calvo, Central G, Sambeat, M A, Gennotte, A F, Payen, M C, Neaton, Central J, El-Sadr, W M, Abrams, D I, Crane, L R, Fischer, A H, Larsen, J F, Wien, Pulmologisches Zentrum der Stadt, Mitsura, V M, Møller, N F, Nielsen, L N, Smidt, Jelena, Siseklinik, Nakkusosakond, Viard, J-P, Stellbrink, H J, Goethe, J W, Sthoeger, Z M, Monforte, A D’Arminio, Annunziata, Ospedale S Maria, Blokhina, I N, Novogrod, Nizhny, Gatell, J M, Miró, J M, Rodriguez, J M, Laporte, J M, Johnson, A M, Johnson, M A, Morfeldt, Central L, Perri, G Di, Marchetti, G C, Perno, C F, Caputo, S Lo, Capobianchi, M R, Biagio, A Di, Roldan, E Quiros, Santoro, M M, Caro, A Di, Manconi, P E, Moioli, M C, Ridolfo, A L, Martino, F Di, Cattelan, A M, Ursitti, M A, Sulekova, L Fontanelli, Plazzi, M M, Del Vecchio, R Fontana, Giuli, C Di, Orofino, G C, Roger, P M, Braun, D L, Bucher, H C, Günthard, H F, Hirsch, H H, Kouyos, R D, de Tejada, B Martinez, Metzner, K J, Scherrer, A U, Valk, Marc vd, Han, W Min, Saint-Pierre, C H U, Miro, J M, Wasmuth, J C, Vehreschild, J J, McNicholl, I, Williams, E D, Volny-Anne, R Campo Alain, Dedes, Nikos, Mendão, Luis, Jakobsen, M L, Kumar, L Ramesh, Elsing, T W, and null, null
Abstract: Background: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. Methods: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. Results: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. Conclusion: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.
Published: 2024

5. Impact of Integrase Inhibitors on Cardiovascular Disease Events in People With Human Immunodeficiency Virus Starting Antiretroviral Therapy

Author: Surial, Bernard; https://orcid.org/0000-0002-1402-974X, Chammartin, Frédérique, Damas, José; https://orcid.org/0000-0001-7724-6226, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Haerry, David, Stöckle, Marcel; https://orcid.org/0000-0002-0088-5078, Schmid, Patrick, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fux, Christoph A, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Wandeler, Gilles; https://orcid.org/0000-0002-5278-8763, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Swiss HIV Cohort Study, Surial, Bernard; https://orcid.org/0000-0002-1402-974X, Chammartin, Frédérique, Damas, José; https://orcid.org/0000-0001-7724-6226, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Haerry, David, Stöckle, Marcel; https://orcid.org/0000-0002-0088-5078, Schmid, Patrick, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fux, Christoph A, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Wandeler, Gilles; https://orcid.org/0000-0002-5278-8763, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, and Swiss HIV Cohort Study
Abstract: BACKGROUND Integrase strand transfer inhibitors (INSTIs) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with human immunodeficiency virus using a target trial framework, which reduces the potential for confounding and selection bias. METHODS We included Swiss HIV Cohort Study participants who were ART-naïve after May 2008, when INSTIs became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (interquartile range, 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increased risk for CVD events (adjusted hazard ratio, 0.80; 95% confidence interval [CI], .46-1.39). Adjusted risk differences between individuals who started INSTIs and those who started other ART were -0.17% (95% CI, -.37 to .19) after 1 year, -0.61% (-1.54 to 0.22) after 5 years, and -0.71% (-2.16 to 0.94) after 8 years. CONCLUSIONS In this target trial emulation, we found no difference in short- or long-term risk for CVD events between treatment-naïve people with human immunodeficiency virus who started INSTI-based ART and those on other ART.
Published: 2023

6. Association of a Polygenic Risk Score With Osteoporosis in People Living With HIV: The Swiss HIV Cohort Study

Author: Schwenke, Johannes M, Thorball, Christian W, Schoepf, Isabella C, Ryom, Lene, Hasse, Barbara, Lamy, Olivier, Calmy, Alexandra, Wandeler, Gilles, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Kahlert, Christian R, Bernasconi, Enos, Kouyos, Roger D, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Ledergerber, Bruno, Fellay, Jacques, Burkhalter, Felix, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Swiss HIV Cohort Study, Schwenke, Johannes M, Thorball, Christian W, Schoepf, Isabella C, Ryom, Lene, Hasse, Barbara, Lamy, Olivier, Calmy, Alexandra, Wandeler, Gilles, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Kahlert, Christian R, Bernasconi, Enos, Kouyos, Roger D, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Ledergerber, Bruno, Fellay, Jacques, Burkhalter, Felix, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, and Swiss HIV Cohort Study
Abstract: BACKGROUND Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH. METHODS Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011-2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements. RESULTS We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34-9.67) and 4.13 (1.86-9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37-3.74), 1.84 (1.40-2.43), and 1.54 (0.82-2.9). CONCLUSIONS In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate.
Published: 2023

7. T-Cell Exhaustion in HIV-1/Hepatitis C Virus Coinfection Is Reduced After Successful Treatment of Chronic Hepatitis C

Author: Caraballo Cortés, Kamila; https://orcid.org/0000-0002-7924-7852, Osuch, Sylwia, Perlejewski, Karol, Radkowski, Marek, Janiak, Maciej, Berak, Hanna, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Fehr, Jan S; https://orcid.org/0000-0003-1113-9895, Hoffmann, Matthias; https://orcid.org/0000-0002-8764-6861, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Caraballo Cortés, Kamila; https://orcid.org/0000-0002-7924-7852, Osuch, Sylwia, Perlejewski, Karol, Radkowski, Marek, Janiak, Maciej, Berak, Hanna, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Fehr, Jan S; https://orcid.org/0000-0003-1113-9895, Hoffmann, Matthias; https://orcid.org/0000-0002-8764-6861, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, and Metzner, Karin J; https://orcid.org/0000-0003-4862-1503
Abstract: BACKGROUND T-cell responses during chronic viral infections become exhausted, which is reflected by upregulation of inhibitory receptors (iRs) and increased interleukin 10 (IL-10). We assessed 2 iRs-PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing protein 3)-and IL-10 mRNAs in peripheral blood mononuclear cells (PBMCs) and their soluble analogs (sPD-1, sTim-3, and IL-10) in plasma in chronic HIV-1/hepatitis C virus (HCV) coinfection and explored the effect of HCV treatment on these markers. We also aimed to establish whether iR expression may be determined by the HCV CD8$^{+}$ T-cell immunodominant epitope sequence. METHODS Plasma and PBMCs from 31 persons with chronic HIV-1/HCV coinfection from the Swiss HIV Cohort Study were collected before and after HCV treatment. As controls, 45 persons who were HIV-1 negative with chronic HCV infection were recruited. Exhaustion markers were assessed by enzyme-linked immunosorbent assay in plasma and by quantitative reverse transcription polymerase chain reaction in PBMCs. Analysis of an HCV epitope sequence was conducted by next-generation sequencing: HLA-A*02-restricted NS3$_{1073-1081}$ and NS3$_{1406-1415}$ and HLA-A*01-restricted NS3$_{1436-1444}$. RESULTS The study revealed higher plasma sPD-1 (P = .0235) and IL-10 (P = .002) levels and higher IL-10 mRNA in PBMCs (P = .0149) in HIV-1/HCV coinfection. A decrease in plasma sPD-1 (P = .0006), sTim-3 (P = .0136), and IL-10 (P = .0003) and Tim-3 mRNA in PBMCs (P = .0210) was observed following successful HCV treatment. Infection with the HLA-A*01-restricted NS3$_{1436-1444}$ ATDALMTGY prototype variant was related to higher sTim-3 levels than infection with the ATDALMTGF escape variant (P = .0326). CONCLUSIONS The results underscore the synergistic effect of coinfection on expression of exhaustion markers, their reduction following successful HCV treatment and imply that iR levels may operate on an epitope-specific manner.
Published: 2023

8. Antibody Response After the Third SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients and People Living With HIV (COVERALL-2)

Author: Griessbach, Alexandra, Chammartin, Frédérique; https://orcid.org/0000-0001-8959-2724, Abela, Irene A, Amico, Patrizia, Stoeckle, Marcel P, Eichenberger, Anna L, Hasse, Barbara, Braun, Dominique L, Schuurmans, Macé M, Müller, Thomas F, Tamm, Michael, Audigé, Annette, Mueller, Nicolas J, Rauch, Andri, Günthard, Huldrych F, Koller, Michael T, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Epp, Selina, Amstutz, Alain, Schönenberger, Christof M, Taji Heravi, Ala, Papadimitriou-Olivgeris, Matthaios, Casutt, Alessio, Manuel, Oriol; https://orcid.org/0000-0001-7607-0943, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Bucher, Heiner C, Briel, Matthias; https://orcid.org/0000-0002-2070-5230, Speich, Benjamin; https://orcid.org/0000-0002-3301-8085, Swiss HIV Cohort Study and the Swiss Transplant Cohort Study, Griessbach, Alexandra, Chammartin, Frédérique; https://orcid.org/0000-0001-8959-2724, Abela, Irene A, Amico, Patrizia, Stoeckle, Marcel P, Eichenberger, Anna L, Hasse, Barbara, Braun, Dominique L, Schuurmans, Macé M, Müller, Thomas F, Tamm, Michael, Audigé, Annette, Mueller, Nicolas J, Rauch, Andri, Günthard, Huldrych F, Koller, Michael T, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Epp, Selina, Amstutz, Alain, Schönenberger, Christof M, Taji Heravi, Ala, Papadimitriou-Olivgeris, Matthaios, Casutt, Alessio, Manuel, Oriol; https://orcid.org/0000-0001-7607-0943, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Bucher, Heiner C, Briel, Matthias; https://orcid.org/0000-0002-2070-5230, Speich, Benjamin; https://orcid.org/0000-0002-3301-8085, and Swiss HIV Cohort Study and the Swiss Transplant Cohort Study
Abstract: BACKGROUND After basic immunization with 2 mRNA SARS-CoV-2 vaccine doses, only a small proportion of patients who are severely immunocompromised generate a sufficient antibody response. Hence, we assessed the additional benefit of a third SARS-CoV-2 vaccine in patients with different levels of immunosuppression. METHODS In this observational extension of the COVERALL trial (Corona Vaccine Trial Platform), we recruited patients from the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study (ie, lung and kidney transplant recipients). We collected blood samples before and 8 weeks after the third SARS-CoV-2 vaccination with either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech). The primary outcome was the proportion of participants showing an antibody response (Elecsys Anti-SARS-CoV-2 S test; threshold ≥100 U/mL) 8 weeks after the third SARS-CoV-2 vaccination. We also compared the proportion of patients who reached the primary outcome from basic immunization (the first and second vaccines) to the third vaccination. RESULTS Nearly all participants (97.2% [95% CI, 95.9%-98.6%], 564/580) had an antibody response. This response was comparable between mRNA-1273 (96.1% [95% CI, 93.7%-98.6%], 245/255) and BNT162b2 (98.2% [95% CI, 96.7%-99.6%], 319/325). Stratification by cohort showed that 99.8% (502/503) of people living with HIV and 80.5% (62/77) of recipients of solid organ transplants achieved the primary endpoint. The proportion of patients with an antibody response in solid organ transplant recipients improved from the second vaccination (22.7%, 15/66) to the third (80.5%, 62/77). CONCLUSIONS People living with HIV had a high antibody response. The third vaccine increased the proportion of solid organ transplant recipients with an antibody response. Clinical Trials Registration. NCT04805125 (ClinicalTrials.gov).
Published: 2023

9. Sustained Viral Suppression With Dolutegravir Monotherapy Over 192 Weeks in Patients Starting Combination Antiretroviral Therapy During Primary Human Immunodeficiency Virus Infection (EARLY-SIMPLIFIED): A Randomized, Controlled, Multi-site, Noninferiority Trial

Author: West, Emily, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Grube, Christina, Kuster, Herbert; https://orcid.org/0000-0001-6873-0091, Wanner, Katrin, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Jörimann, Lisa; https://orcid.org/0009-0006-3076-2999, Hampel, Benjamin, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, West, Emily, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Grube, Christina, Kuster, Herbert; https://orcid.org/0000-0001-6873-0091, Wanner, Katrin, Scheier, Thomas; https://orcid.org/0000-0001-7805-1025, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Jörimann, Lisa; https://orcid.org/0009-0006-3076-2999, Hampel, Benjamin, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, and Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723
Abstract: BACKGROUND: Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a 4-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy. METHODS: EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. People with HIV (PWH) who started cART <180 days after a documented primary HIV-1 infection with suppressed viral load were randomized (2:1) to DTG monotherapy with 50 mg daily or continuation of cART. The primary endpoints were the proportion of PWH with viral failure at 48, 96, 144, and 192 weeks; noninferiority margin was 10%. After 96 weeks, randomization was lifted and patients were permitted to switch treatment groups as desired. RESULTS: Of 101 PWH randomized, 68 were assigned to DTG monotherapy and 33 to cART. At week 96 in the per-protocol population, 64/64 (100%) showed virological response in the DTG monotherapy group versus 30/30 (100%) in the cART group (difference, 0.00%; upper bound of 95% confidence interval 6.22%). This demonstrated noninferiority of DTG monotherapy at the prespecified level. At week 192, the study end, no virological failure occurred in either group during 13 308 and 4897 person weeks of follow-up for the DTG monotherapy (n = 80) and cART groups, respectively. CONCLUSIONS: This trial suggests that early cART initiation during primary HIV infection allows sustained virological suppression after switching to DTG monotherapy.
Published: 2023

10. Antibody Response After Third Vaccination With mRNA-1273 or BNT162b2: Extension of a Randomized Controlled SARS-CoV-2 Noninferiority Vaccine Trial in Patients With Different Levels of Immunosuppression (COVERALL-2)

Author: Griessbach, Alexandra; https://orcid.org/0000-0003-3726-1856, Chammartin, Frédérique, Abela, Irene A, Amico, Patrizia, Stoeckle, Marcel P, Eichenberger, Anna L, Hasse, Barbara; https://orcid.org/0000-0001-7196-3734, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Schuurmans, Macé Matthew; https://orcid.org/0000-0001-5404-7566, Müller, Thomas F; https://orcid.org/0000-0003-2236-2312, Tamm, Michael, Audigé, Annette, Mueller, Nicolas J; https://orcid.org/0000-0002-1059-3191, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Koller, Michael T, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Epp, Selina, Amstutz, Alain; https://orcid.org/0000-0003-1716-993X, Schönenberger, Christof M, Taji Heravi, Ala; https://orcid.org/0000-0003-3752-1611, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Bucher, Heiner C; https://orcid.org/0000-0002-0131-7873, Briel, Matthias; https://orcid.org/0000-0002-2070-5230, Speich, Benjamin; https://orcid.org/0000-0002-3301-8085, Swiss HIV Cohort Study and the Swiss Transplant Cohort Study, Griessbach, Alexandra; https://orcid.org/0000-0003-3726-1856, Chammartin, Frédérique, Abela, Irene A, Amico, Patrizia, Stoeckle, Marcel P, Eichenberger, Anna L, Hasse, Barbara; https://orcid.org/0000-0001-7196-3734, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Schuurmans, Macé Matthew; https://orcid.org/0000-0001-5404-7566, Müller, Thomas F; https://orcid.org/0000-0003-2236-2312, Tamm, Michael, Audigé, Annette, Mueller, Nicolas J; https://orcid.org/0000-0002-1059-3191, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Koller, Michael T, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Epp, Selina, Amstutz, Alain; https://orcid.org/0000-0003-1716-993X, Schönenberger, Christof M, Taji Heravi, Ala; https://orcid.org/0000-0003-3752-1611, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Bucher, Heiner C; https://orcid.org/0000-0002-0131-7873, Briel, Matthias; https://orcid.org/0000-0002-2070-5230, Speich, Benjamin; https://orcid.org/0000-0002-3301-8085, and Swiss HIV Cohort Study and the Swiss Transplant Cohort Study
Abstract: Extension of the COVERALL (COrona VaccinE tRiAL pLatform) randomized trial showed noninferiority in antibody response of the third dose of Moderna mRNA-1273 vaccine (95.3% [95% confidence interval {CI}, 91.9%-98.7%]) compared to Pfizer-BioNTech BNT162b2 vaccine (98.1% [95% CI, 95.9%-100.0%]) in individuals with different levels of immunosuppression (difference, -2.8% [95% CI, -6.8% to 1.3%]).
Published: 2023

11. Understanding the decline of incident, active tuberculosis in people with HIV in Switzerland

Author: Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Tepekule, Burcu; https://orcid.org/0000-0001-6936-9138, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Reiber, Claudine, Kälin, Marisa, Bartl, Lena, Notter, Julia, Furrer, Hansjakob; https://orcid.org/0000-0002-1375-3146, Hoffmann, Matthias; https://orcid.org/0000-0002-8764-6861, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Nemeth, Johannes; https://orcid.org/0000-0003-0683-456X, Swiss HIV Cohort Study, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Tepekule, Burcu; https://orcid.org/0000-0001-6936-9138, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Reiber, Claudine, Kälin, Marisa, Bartl, Lena, Notter, Julia, Furrer, Hansjakob; https://orcid.org/0000-0002-1375-3146, Hoffmann, Matthias; https://orcid.org/0000-0002-8764-6861, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Nemeth, Johannes; https://orcid.org/0000-0003-0683-456X, and Swiss HIV Cohort Study
Abstract: BACKGROUND: People with human immunodeficiency virus type 1 (HIV) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear. METHODS: We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS). The outcome, incident TB, was defined as TB ≥6 months after SHCS inclusion. We assessed its risk factors using a time-updated hazard regression, modeled the potential impact of modifiable factors on TB incidence, performed mediation analysis to assess underlying causes of time trends, and evaluated preventive measures. RESULTS: In 21,528 PWH, LTBI prevalence declined from 15.1% in 2001 to 4.6% in 2021. Incident TB declined from 90.8 cases/1000 person-years in 1989 to 0.1 in 2021. A positive LTBI test showed a higher risk for incident TB (HR 9.8, 5.8-16.5) but only 10.5% of PWH with incident TB were tested positive. Preventive treatment reduced the risk in LTBI test positive PWH for active TB (relative risk reduction, 28.1%, absolute risk reduction 0.9%). On population level, the increase of CD4 T-cells and reduction of HIV viral load were the main driver of TB decrease. CONCLUSIONS: TB specific prevention is effective in selected patient groups. On a population level, control of HIV-1 remains the most important factor for incident TB reduction. Accurate identification of PWH at highest risk for TB is an unmet clinical need.
Published: 2023

12. Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018

Author: Jaha, Bashkim, Schenkel, Corinne D, Jörimann, Lisa, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Zaheri, Maryam; https://orcid.org/0000-0003-2777-835X, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Leemann, Christine, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Swiss HIV Cohort Study, Jaha, Bashkim, Schenkel, Corinne D, Jörimann, Lisa, Huber, Michael; https://orcid.org/0000-0002-0384-0000, Zaheri, Maryam; https://orcid.org/0000-0003-2777-835X, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Leemann, Christine, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, and Swiss HIV Cohort Study
Abstract: BACKGROUND: Genotypic resistance testing (GRT) is routinely performed upon diagnosis of HIV-1 infection or during virological failure using plasma viral RNA. An alternative source for GRT could be cellular HIV-1 DNA. OBJECTIVES: A substantial number of participants in the Swiss HIV Cohort Study (SHCS) never received GRT. We applied a method that enables access to the near full-length proviral HIV-1 genome without requiring detectable viraemia. METHODS: Nine hundred and sixty-two PBMC specimens were received. Our two-step nested PCR protocol was applied to generate two overlapping long-range amplicons of the HIV-1 genome, sequenced by next-generation sequencing (NGS) and analysed by MinVar, a pipeline to detect drug resistance mutations (DRMs). RESULTS: Six hundred and eighty-one (70.8%) of the samples were successfully amplified, sequenced and analysed by MinVar. Only partial information of the pol gene was contained in 82/681 (12%), probably due to naturally occurring deletions in the proviral sequence. All common HIV-1 subtypes were successfully sequenced. We detected at least one major DRM at high frequency (≥15%) in 331/599 (55.3%) individuals. Excluding APOBEC-signature (G-to-A mutation) DRMs, 145/599 (24.2%) individuals carried at least one major DRM. RT-inhibitor DRMs were most prevalent. The experienced time on ART was significantly longer in DRM carriers (P = 0.001) independent of inclusion or exclusion of APOBEC-signature DRMs. CONCLUSIONS: We successfully applied a reliable and efficient method to analyse near full-length HIV-1 proviral DNA and investigated DRMs in individuals with undetectable or low viraemia. Additionally, our data underscore the need for new computational tools to exclude APOBEC-related hypermutated NGS sequence reads for reporting DRMs.
Published: 2023

13. Leukocyte Count and Coronary Artery Disease Events in People With Human Immunodeficiency Virus: A Longitudinal Study

Author: Avery, Emma F, Kleynhans, Julia N, Ledergerber, Bruno; https://orcid.org/0000-0002-6881-4401, Schoepf, Isabella C, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Kootstra, Neeltje A, Reiss, Peter; https://orcid.org/0000-0001-7896-6428, Ryom, Lene, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Thurnheer, Maria Christine; https://orcid.org/0000-0003-1357-0347, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Seneghini, Marco, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Buvelot, Hélène, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Swiss HIV Cohort Study, Avery, Emma F, Kleynhans, Julia N, Ledergerber, Bruno; https://orcid.org/0000-0002-6881-4401, Schoepf, Isabella C, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Kootstra, Neeltje A, Reiss, Peter; https://orcid.org/0000-0001-7896-6428, Ryom, Lene, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Thurnheer, Maria Christine; https://orcid.org/0000-0003-1357-0347, Marzolini, Catia; https://orcid.org/0000-0002-2312-7050, Seneghini, Marco, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Buvelot, Hélène, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, and Swiss HIV Cohort Study
Abstract: BACKGROUND: People with human immunodeficiency virus (HIV; PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. METHODS: In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. RESULTS: We included 536 cases with a first CAD event (2000-2021; median age, 56 years; 87% male; 84% with suppressed HIV RNA) and 1464 event-free controls. Cases had higher latest leukocyte count before CAD event than controls (median [interquartile range], 6495 [5300-7995] vs 5900 [4910-7200]; P < .01), but leukocytosis (>11 000/µL) was uncommon (4.3% vs 2.1%; P = .01). In the highest versus lowest leukocyte quintile at latest time point before CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years before the event were significantly associated with CAD events. CONCLUSIONS: PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.
Published: 2023

14. Absence of Proviral Human Immunodeficiency Virus (HIV) Type 1 Evolution in Early-Treated Individuals With HIV Switching to Dolutegravir Monotherapy During 48 Weeks

Author: Jörimann, Lisa; https://orcid.org/0009-0006-3076-2999, Tschumi, Jasmin, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Leemann, Christine, Schenkel, Corinne D, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Chaudron, Sandra E; https://orcid.org/0000-0002-1385-1854, Zaheri, Maryam; https://orcid.org/0000-0003-2777-835X, Frischknecht, Paul, Neuner-Jehle, Nadia, Kuster, Herbert; https://orcid.org/0000-0001-6873-0091, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Grube, Christina, Kouyos, Roger; https://orcid.org/0000-0002-9220-8348, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Swiss HIV Cohort Study (SHCS), Jörimann, Lisa; https://orcid.org/0009-0006-3076-2999, Tschumi, Jasmin, Zeeb, Marius; https://orcid.org/0000-0001-6822-1473, Leemann, Christine, Schenkel, Corinne D, Neumann, Kathrin; https://orcid.org/0000-0001-5034-6999, Chaudron, Sandra E; https://orcid.org/0000-0002-1385-1854, Zaheri, Maryam; https://orcid.org/0000-0003-2777-835X, Frischknecht, Paul, Neuner-Jehle, Nadia, Kuster, Herbert; https://orcid.org/0000-0001-6873-0091, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Grube, Christina, Kouyos, Roger; https://orcid.org/0000-0002-9220-8348, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, and Swiss HIV Cohort Study (SHCS)
Abstract: Human immunodeficiency virus type 1 (HIV-1) infection is treated with antiretroviral therapy (ART), usually consisting of 2-3 different drugs, referred to as combination ART (cART). Our recent randomized clinical trial comparing a switch to dolutegravir monotherapy with continuation of cART in early-treated individuals demonstrated sustained virological suppression over 48 weeks. Here, we characterize the longitudinal landscape of the HIV-1 reservoir in these participants, with particular attention to potential differences between treatment groups regarding evidence of evolution as a proxy for low-level replication. Near full-length HIV-1 proviral polymerase chain reaction and next-generation sequencing was applied to longitudinal peripheral blood mononuclear cell samples to assess proviral evolution and the potential emergence of drug resistance mutations (DRMs). Neither an increase in genetic distance nor diversity over time was detected in participants of both treatment groups. Single proviral analysis showed high proportions of defective proviruses and low DRM numbers. No evidence for evolution during dolutegravir monotherapy was found in these early-treated individuals.
Published: 2023

15. Seroprofiling of Antibodies Against Endemic Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 in a Human Immunodeficiency Virus Cohort in Lesotho: Correlates of Antibody Response and Seropositivity

Author: Brown, Jennifer A; https://orcid.org/0000-0003-1874-6153, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Epp, Selina, Mohloanyane, Tsepang; https://orcid.org/0000-0002-8530-1499, Nsakala, Bienvenu L, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Brown, Jennifer A; https://orcid.org/0000-0003-1874-6153, Hauser, Anthony; https://orcid.org/0000-0002-7221-1929, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Pasin, Chloé; https://orcid.org/0000-0001-8730-790X, Epp, Selina, Mohloanyane, Tsepang; https://orcid.org/0000-0002-8530-1499, Nsakala, Bienvenu L, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, and Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723
Abstract: BACKGROUND: Serological data on endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Africa are scarce. Here, we report on (1) endemic HCoV seasonality, (2) SARS-CoV-2 seroprevalence, and (3) correlates of SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and endemic HCoV serological responses among adults living with human immunodeficiency virus (HIV). METHODS: Plasma samples were collected from February 2020 to July 2021 within an HIV cohort in Lesotho. We used the AntiBody CORonavirus Assay (ABCORA) multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS: Results for 3173 samples from 1403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter and spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex, obesity, working outside the home, and recent tiredness or fever. Positive correlations were observed between the strength of response to endemic HCoVs and to SARS-CoV-2 and between older age or obesity and the immunoglobulin G response to SARS-CoV-2. CONCLUSIONS: These results add to our understanding of the impact of biological, clinical, and social/behavioral factors on serological responses to coronaviruses in southern Africa.
Published: 2023

16. Triggers of change in sexual behavior among people with HIV: The Swiss U = U statement and Covid-19 compared

Author: Hamusonde, Kalongo, Nicca, Dunja; https://orcid.org/0000-0002-4133-8177, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Stöckle, Marcel; https://orcid.org/0000-0002-0088-5078, Darling, Katharine Ea; https://orcid.org/0000-0003-1449-3873, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Haerry, David, Schmid, Patrick, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Salazar-Vizcaya, Luisa; https://orcid.org/0000-0003-0527-0141, Swiss HIV Cohort Study, Hamusonde, Kalongo, Nicca, Dunja; https://orcid.org/0000-0002-4133-8177, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Stöckle, Marcel; https://orcid.org/0000-0002-0088-5078, Darling, Katharine Ea; https://orcid.org/0000-0003-1449-3873, Calmy, Alexandra; https://orcid.org/0000-0002-1137-6826, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Haerry, David, Schmid, Patrick, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Salazar-Vizcaya, Luisa; https://orcid.org/0000-0003-0527-0141, and Swiss HIV Cohort Study
Abstract: We assessed changes in sexual behaviour among people with HIV (PWH) over 20 years. Condom use with stable partners steadily declined from over 90% to 29% since the Swiss U = U statement with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during COVID-19 social distancing.
Published: 2023

17. Seroprofiling of antibodies against endemic human coronaviruses and SARS-CoV-2 in an HIV cohort in Lesotho: correlates of antibody response and seropositivity

Author: Brown, Jennifer A, Hauser, Anthony, Abela, Irene A, Pasin, Chloé, Epp, Selina, Mohloanyane, Tsepang, Nsakala, Bienvenu L, Trkola, Alexandra, Labhardt, Niklaus D, Kouyos, Roger D, and Günthard, Huldrych F
Subjects: 360 Social problems & social services, 610 Medicine & health
Abstract: BACKGROUND Serological data on endemic human coronaviruses (HCoVs) and SARS-CoV-2 in southern Africa are scarce. Here, we report on i) endemic HCoV seasonality, ii) SARS-CoV-2 seroprevalence, and iii) predictive factors for SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and HCoV serological response during a 17-month period at the start of the COVID-19 pandemic among adults living with HIV. METHODS Plasma samples were collected from February 2020 to July 2021 within an outpatient HIV cohort in Lesotho. We used the ABCORA multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. RESULTS Results of 3'173 samples from 1'403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter/spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex (p = 0.004), obesity (p
Published: 2023
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18. Leukocyte Count and Coronary Artery Disease Events in People with HIV: A Longitudinal Study

Author: Avery, Emma F, Kleynhans, Julia N, Ledergerber, Bruno, Schoepf, Isabella C, Thorball, Christian W, Kootstra, Neeltje A, Reiss, Peter, Ryom, Lene, Braun, Dominique L, Thurnheer, Maria C, Marzolini, Catia, Seneghini, Marco, Bernasconi, Enos, Cavassini, Matthias, Buvelot, Hélène, Kouyos, Roger D, Fellay, Jacques, Günthard, Huldrych F, and Tarr, Philip E
Subjects: 610 Medizin und Gesundheit
Abstract: BACKGROUND People with HIV (PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. METHODS In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. RESULTS We included 536 cases with a first CAD event (2000-2021; median age 56 years, 87% male, 84% with suppressed HIV-RNA) and 1464 event-free controls. Cases had higher latest leukocyte count prior to CAD event than controls (median [interquartile range], 6495 [5300-7995] vs. 5900 [4910-7200]; p 11000/uL) was uncommon (4.3% vs. 2.1%; p = 0.01). In the highest vs. lowest leukocyte quintile at latest time point prior to CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years pre-event were significantly associated with CAD events. CONCLUSIONS PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.
Published: 2023
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19. Antibody Response After Third Vaccination With mRNA-1273 or BNT162b2: Extension of a Randomized Controlled SARS-CoV-2 Noninferiority Vaccine Trial in Patients With Different Levels of Immunosuppression (COVERALL-2)

Author: Griessbach, Alexandra, Chammartin, Frédérique, Abela, Irene A, Amico, Patrizia, Stoeckle, Marcel P, Eichenberger, Anna L, Hasse, Barbara, Braun, Dominique L, Schuurmans, Macé M, Müller, Thomas F, Tamm, Michael, Audigé, Annette, Mueller, Nicolas J, Rauch, Andri, Günthard, Huldrych F, Koller, Michael T, Trkola, Alexandra, Epp, Selina, Amstutz, Alain, Schönenberger, Christof M, Taji Heravi, Ala, Kusejko, Katharina, Bucher, Heiner C, Briel, Matthias, and Speich, Benjamin
Subjects: 610 Medicine & health
Abstract: Extension of the COVERALL (COrona VaccinE tRiAL pLatform) randomized trial showed noninferiority in antibody response of the third dose of Moderna mRNA-1273 vaccine (95.3% [95% confidence interval {CI}, 91.9%-98.7%]) compared to Pfizer-BioNTech BNT162b2 vaccine (98.1% [95% CI, 95.9%-100.0%]) in individuals with different levels of immunosuppression (difference, -2.8% [95% CI, -6.8% to 1.3%]).
Published: 2023
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20. Impact of integrase inhibitors on cardiovascular disease events in people with HIV starting antiretroviral therapy

Author: Surial, Bernard, Chammartin, Frédérique, Damas, José, Calmy, Alexandra, Haerry, David, Stöckle, Marcel, Schmid, Patrick, Bernasconi, Enos, Fux, Christoph A, Tarr, Philip, Günthard, Huldrych F, Wandeler, Gilles, and Rauch, Andri
Subjects: 610 Medicine & health
Abstract: BACKGROUND Integrase strand transfer inhibitors (INSTI) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with HIV (PWH) using a target trial framework, which reduces the potential for confounding and selection bias. METHODS We included Swiss HIV Cohort Study participants who were ART-naïve after 05/2008, when INSTI became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs. other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (IQR 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increase in CVD events (adjusted hazard ratio 0.80, 95% confidence interval [CI] 0.46-1.39). Adjusted risk differences between individuals who started INSTI and those who started other ART were -0.17% (95% CI -0.37-0.19) after one year, -0.61% (-1.54-0.22) after 5 years, and -0.71% (-2.16-0.94) after 8 years. CONCLUSIONS In this target trial emulation, we found no difference in short or longer term risk for CVD events between treatment-naïve PWH who started INSTI-based and those on other ART.
Published: 2023
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21. Quantifying and predicting ongoing Human Immunodeficiency Virus Type 1 (HIV-1) transmission dynamics in Switzerland using a distance-based clustering approach

Author: Labarile, Marco, Loosli, Tom, Zeeb, Marius, Kusejko, Katharina, Huber, Michael, Hirsch, Hans H, Perreau, Matthieu, Ramette, Alban, Yerly, Sabine, Cavassini, Matthias, Battegay, Manuel, Rauch, Andri, Calmy, Alexandra, Notter, Julia, Bernasconi, Enos, Fux, Christoph, Günthard, Huldrych F, Pasin, Chloé, Kouyos, Roger D, Swiss HIV Cohort Study, and University of Zurich
Subjects: 10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 570 Life sciences, biology, 610 Medicine & health
Published: 2023
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22. Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1

Author: Balakrishna, Suraj, Loosli, Tom, Zaheri, Maryam, Frischknecht, Paul, Huber, Michael, Kusejko, Katharina, Yerly, Sabine, Leuzinger, Karoline, Perreau, Matthieu, Ramette, Alban, Wymant, Chris, Fraser, Christophe, Kellam, Paul, Gall, Astrid, Hirsch, Hans H, Stoeckle, Marcel, Rauch, Andri, Cavassini, Matthias, Bernasconi, Enos, Notter, Julia, Calmy, Alexandra, Günthard, Huldrych F, Metzner, Karin J, and Kouyos, Roger D
Subjects: Pharmacology, Microbiology (medical), Infectious Diseases, Pharmacology (medical), 610 Medizin und Gesundheit, 570 Biowissenschaften, Biologie
Abstract: BackgroundNext-generation sequencing (NGS) is gradually replacing Sanger sequencing (SS) as the primary method for HIV genotypic resistance testing. However, there are limited systematic data on comparability of these methods in a clinical setting for the presence of low-abundance drug resistance mutations (DRMs) and their dependency on the variant-calling thresholds.MethodsTo compare the HIV-DRMs detected by SS and NGS, we included participants enrolled in the Swiss HIV Cohort Study (SHCS) with SS and NGS sequences available with sample collection dates ≤7 days apart. We tested for the presence of HIV-DRMs and compared the agreement between SS and NGS at different variant-calling thresholds.ResultsWe included 594 pairs of SS and NGS from 527 SHCS participants. Males accounted for 80.5% of the participants, 76.3% were ART naive at sample collection and 78.1% of the sequences were subtype B. Overall, we observed a good agreement (Cohen’s kappa >0.80) for HIV-DRMs for variant-calling thresholds ≥5%. We observed an increase in low-abundance HIV-DRMs detected at lower thresholds [28/417 (6.7%) at 10%–25% to 293/812 (36.1%) at 1%–2% threshold]. However, such low-abundance HIV-DRMs were overrepresented in ART-naive participants and were in most cases not detected in previously sampled sequences suggesting high sequencing error for thresholds ConclusionsWe found high concordance between SS and NGS but also a substantial number of low-abundance HIV-DRMs detected only by NGS at lower variant-calling thresholds. Our findings suggest that a substantial fraction of the low-abundance HIV-DRMs detected at thresholds
Published: 2023
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23. Understanding the decline of incident, active tuberculosis in people with HIV in Switzerland

Author: Zeeb, Marius, Tepekule, Burcu, Kusejko, Katharina, Reiber, Claudine, Kälin, Marisa, Bartl, Lena, Notter, Julia, Furrer, Hansjakob, Hoffmann, Matthias, Hirsch, Hans H, Calmy, Alexandra, Cavassini, Matthias, Labhardt, Niklaus D, Bernasconi, Enos, Braun, Dominique L, Günthard, Huldrych F, Kouyos, Roger D, and Nemeth, Johannes
Subjects: 610 Medicine & health
Abstract: BACKGROUND People with human immunodeficiency virus type 1 (HIV) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear. METHODS We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS). The outcome, incident TB, was defined as TB ≥6 months after SHCS inclusion. We assessed its risk factors using a time-updated hazard regression, modeled the potential impact of modifiable factors on TB incidence, performed mediation analysis to assess underlying causes of time trends, and evaluated preventive measures. RESULTS In 21,528 PWH, LTBI prevalence declined from 15.1% in 2001 to 4.6% in 2021. Incident TB declined from 90.8 cases/1000 person-years in 1989 to 0.1 in 2021. A positive LTBI test showed a higher risk for incident TB (HR 9.8, 5.8-16.5) but only 10.5% of PWH with incident TB were tested positive. Preventive treatment reduced the risk in LTBI test positive PWH for active TB (relative risk reduction, 28.1%, absolute risk reduction 0.9%). On population level, the increase of CD4 T-cells and reduction of HIV viral load were the main driver of TB decrease. CONCLUSIONS TB specific prevention is effective in selected patient groups. On a population level, control of HIV-1 remains the most important factor for incident TB reduction. Accurate identification of PWH at highest risk for TB is an unmet clinical need.
Published: 2023
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24. A Phylogeny-aware GWAS Framework to Correct for Heritable Pathogen Effects on Infectious Disease Traits

Author: Nadeau, Sarah; https://orcid.org/0000-0003-1008-8918, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Kouyos, Roger; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Yerly, Sabine; https://orcid.org/0000-0003-1668-696X, Perreau, Matthieu, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Vernazza, Pietro; https://orcid.org/0000-0002-6849-6941, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Mitov, Venelin; https://orcid.org/0000-0002-5227-5191, Stadler, Tanja; https://orcid.org/0000-0001-6431-535X, Swiss HIV Cohort Study (SHCS), Nadeau, Sarah; https://orcid.org/0000-0003-1008-8918, Thorball, Christian W; https://orcid.org/0000-0002-6869-6943, Kouyos, Roger; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Böni, Jürg; https://orcid.org/0000-0001-7925-4852, Yerly, Sabine; https://orcid.org/0000-0003-1668-696X, Perreau, Matthieu, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Hirsch, Hans H; https://orcid.org/0000-0003-0883-0423, Cavassini, Matthias; https://orcid.org/0000-0003-0933-7833, Vernazza, Pietro; https://orcid.org/0000-0002-6849-6941, Bernasconi, Enos; https://orcid.org/0000-0002-9724-8373, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Mitov, Venelin; https://orcid.org/0000-0002-5227-5191, Stadler, Tanja; https://orcid.org/0000-0001-6431-535X, and Swiss HIV Cohort Study (SHCS)
Abstract: Infectious diseases are particularly challenging for genome-wide association studies (GWAS) because genetic effects from two organisms (pathogen and host) can influence a trait. Traditional GWAS assume individual samples are independent observations. However, pathogen effects on a trait can be heritable from donor to recipient in transmission chains. Thus, residuals in GWAS association tests for host genetic effects may not be independent due to shared pathogen ancestry. We propose a new method to estimate and remove heritable pathogen effects on a trait based on the pathogen phylogeny prior to host GWAS, thus restoring independence of samples. In simulations, we show this additional step can increase GWAS power to detect truly associated host variants when pathogen effects are highly heritable, with strong phylogenetic correlations. We applied our framework to data from two different host-pathogen systems, HIV in humans and X. arboricola in A. thaliana. In both systems, the heritability and thus phylogenetic correlations turn out to be low enough such that qualitative results of GWAS do not change when accounting for the pathogen shared ancestry through a correction step. This means that previous GWAS results applied to these two systems should not be biased due to shared pathogen ancestry. In summary, our framework provides additional information on the evolutionary dynamics of traits in pathogen populations and may improve GWAS if pathogen effects are highly phylogenetically correlated amongst individuals in a cohort.
Published: 2022

25. Phylogenetic estimation of the viral fitness landscape of HIV-1 set-point viral load

Author: Zhao, Lele; https://orcid.org/0000-0002-2807-1914, Wymant, Chris; https://orcid.org/0000-0002-9847-8226, Blanquart, François; https://orcid.org/0000-0003-0591-2466, Golubchik, Tanya; https://orcid.org/0000-0003-2765-9828, Gall, Astrid, Bakker, Margreet, Bezemer, Daniela; https://orcid.org/0000-0001-9304-0877, Hall, Matthew, Ong, Swee Hoe; https://orcid.org/0000-0002-3629-5387, Albert, Jan, Bannert, Norbert, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Grabowski, M Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kivelä, Pia, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, van Sighem, Ard; https://orcid.org/0000-0002-6656-0516, van der Valk, Marc, Berkhout, Ben; https://orcid.org/0000-0002-1905-8486, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Ferretti, Luca; https://orcid.org/0000-0001-7578-7301, Zhao, Lele; https://orcid.org/0000-0002-2807-1914, Wymant, Chris; https://orcid.org/0000-0002-9847-8226, Blanquart, François; https://orcid.org/0000-0003-0591-2466, Golubchik, Tanya; https://orcid.org/0000-0003-2765-9828, Gall, Astrid, Bakker, Margreet, Bezemer, Daniela; https://orcid.org/0000-0001-9304-0877, Hall, Matthew, Ong, Swee Hoe; https://orcid.org/0000-0002-3629-5387, Albert, Jan, Bannert, Norbert, Fellay, Jacques; https://orcid.org/0000-0002-8240-939X, Grabowski, M Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kivelä, Pia, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, van Sighem, Ard; https://orcid.org/0000-0002-6656-0516, van der Valk, Marc, Berkhout, Ben; https://orcid.org/0000-0002-1905-8486, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, and Ferretti, Luca; https://orcid.org/0000-0001-7578-7301
Abstract: Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical optimum for the virus between 10$^{4}$ and 10$^{5}$ copies of viral RNA per ml. Here we aimed to detect transmission fitness differences between viruses from individuals with different SPVLs directly from phylogenetic trees inferred from whole-genome sequences. We used the local branching index (LBI) as a proxy for transmission fitness. We found that LBI is more sensitive to differences in infectiousness than to differences in the duration of the infectious state. By analysing subtype-B samples from the Bridging the Evolution and Epidemiology of HIV in Europe project, we inferred a significant positive relationship between SPVL and LBI up to approximately 10$^{5}$ copies/ml, with some evidence for a peak around this value of SPVL. This is evidence of selection against low values of SPVL in HIV-1 subtype-B strains, likely related to lower infectiousness, and perhaps a peak in the transmission fitness in the expected range of SPVL. The less prominent signatures of selection against higher SPVL could be explained by an inherent limit of the method or the deployment of antiretroviral therapy.
Published: 2022

26. Factors Associated With Liver Steatosis in People With Human Immunodeficiency Virus on Contemporary Antiretroviral Therapy

Author: Riebensahm, Carlotta, Berzigotti, Annalisa, Surial, Bernard, Günthard, Huldrych F, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Furrer, Hansjakob, Rauch, Andri, Wandeler, Gilles, Swiss HIV Cohort Study, Riebensahm, Carlotta, Berzigotti, Annalisa, Surial, Bernard, Günthard, Huldrych F, Tarr, Philip E; https://orcid.org/0000-0002-1488-5407, Furrer, Hansjakob, Rauch, Andri, Wandeler, Gilles, and Swiss HIV Cohort Study
Abstract: Background: Given the impact of new antiretroviral drugs on weight and metabolic parameters, their potential contribution to the development of liver steatosis is of concern. We investigated the determinants of liver steatosis in patients on antiretroviral therapy (ART) in the Swiss HIV Cohort Study (SHCS). Methods: Between 2019 and 2021, we measured liver stiffness and controlled attenuation parameter (CAP) using transient elastography in consecutive SHCS participants at Bern University Hospital. Individuals with viral hepatitis coinfection and pregnant women were excluded. We used multivariable logistic regression to explore factors associated with steatosis. Results: Of 416 participants, 113 (27.2%) were female, median age was 51 years (interquartile range [IQR], 43-59), 305 (73.3%) were of European origin, and 212 (51.0%) were overweight/obese (body mass index [BMI] ≥25 kg/m2). Liver steatosis (CAP ≥248 dB/m) was present in 212 (51.0%) participants, 11 (5.2%) of whom had significant fibrosis or cirrhosis. One hundred seventy-nine (43.0%) met the criteria for metabolic-associated fatty liver disease (MAFLD). Among 64 individuals with a BMI <25 kg/m2 and liver steatosis, 31 (48.4%) had MAFLD. In multivariable analyses, BMI ≥25 kg/m2 (adjusted odds ratio, 5.76; 95% confidence interval, 3.57-9.29), age ≥50 years (1.88, 1.14-3.09), European origin (3.16, 1.69-5.89), and current use of tenofovir alafenamide (1.70, 1.08-2.69) were associated with liver steatosis. Exposure to integrase inhibitors was not associated with liver steatosis (0.83, 0.51-1.37). Conclusions: Our findings suggest a high prevalence of liver steatosis among people with HIV (PWH) on ART in Switzerland. In addition to established risk factors, the use of tenofovir alafenamide was associated with hepatic steatosis. Keywords: antiretroviral therapy; liver steatosis; metabolic comorbidities; metabolic-associated fatty liver disease; people with HIV.
Published: 2022

27. Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting

Author: Greenberg, Lauren, Ryom, Lene, Neesgaard, Bastian, et al, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Greenberg, Lauren, Ryom, Lene, Neesgaard, Bastian, et al, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, and Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940
Abstract: BACKGROUND Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure. METHODS Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months. RESULTS Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36-51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9-7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3-7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi's sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89-1.49], >6-12 months; 0.97 [95% CI, 0.71-1.32], >12-24 months; 0.84 [95% CI, 0.64-1.11], >24-36 months; 1.10 [95% CI, 0.82-1.47], >36 months; 0.90 [95% CI, 0.65-1.26] [P = .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P < .0001). CONCLUSIONS Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding.
Published: 2022

28. High Rates of Asymptomatic Mycoplasma genitalium Infections With High Proportion of Genotypic Resistance to First-Line Macrolide Treatment Among Men Who Have Sex With Men Enrolled in the Zurich Primary HIV Infection Study

Author: Ring, Alexander; https://orcid.org/0000-0002-0092-1323, Balakrishna, Suraj, Imkamp, Frank, Burkard, Sara, Triet, Flurina, Brunschweiler, Flurina, Grube, Christina, Bodmer, Rebecca, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F, Braun, Dominique L, Ring, Alexander; https://orcid.org/0000-0002-0092-1323, Balakrishna, Suraj, Imkamp, Frank, Burkard, Sara, Triet, Flurina, Brunschweiler, Flurina, Grube, Christina, Bodmer, Rebecca, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Günthard, Huldrych F, and Braun, Dominique L
Abstract: Background Mycoplasma genitalium (Mg) is an emerging sexually transmitted pathogen among men who have sex with men (MSM). Resistance to recommended antimicrobial agents are of public health concern. Few data exist on Mg infections in MSM diagnosed with human immunodeficiency virus (HIV) during primary HIV infection. Methods Participants of the Zurich Primary HIV Study (ClinicalTrials.gov Identifier NCT00537966) were systematically offered screening for sexually transmitted infections (STIs) between April 2019 and September 2020. Screening was performed using an in-house polymerase chain reaction panel comprising Mg including genotypic resistance testing for macrolides and quinolones, Chlamydia trachomatis including serovars L1-L3, Neisseria gonorrhoeae, Treponema pallidum, and Hemophilus ducreyi. Results We screened 148 of 266 (55.6%) participants, with an overall total of 415 follow-up visits. Ninety-one percent were MSM. The incidence rate for all STIs was 47.0 (95% confidence interval [CI], 32.2-68.6) per 100 person-years. Mycoplasma genitalium was the most frequently detected pathogen: 30 participants (20%) presented with at least 1 Mg infection, corresponding to a period prevalence of 20.3% and incidence rate of 19.5 Mg infections (95% CI, 11.8-32.4). Most Mg infections (93%) were asymptomatic, and 9 (30%) participants showed spontaneous clearance. We detected high rates of antibiotic resistance: 73.3% to macrolides, 3.3% to quinolones, and 13.3% resistance to both antibiotics. Conclusions The high prevalence of mostly asymptomatic Mg infections and high rate of spontaneous clearance support cautious initiation for treatment. The high proportion of macrolide-resistant strains suggests that a genotypic determination of resistance should be standard of care. Moxifloxacin should be the preferred treatment option for symptomatic Mg infections among MSM if resistance testing is unavailable.
Published: 2022

29. Dolutegravir Monotherapy as Maintenance Strategy: A Meta-Analysis of Individual Participant Data From Randomized Controlled Trials

Author: Fournier, Anna L, Hocqueloux, Laurent, Braun, Dominique L, Metzner, Karin J, Kouyos, Roger D, Raffi, François, Briant, Anaïs R, Martinez, Esteban, De Lazzari, Elisa, Negredo, Eugenia, Rijnders, Bart, Rokx, Casper, Günthard, Huldrych F, Parienti, Jean-Jacques; https://orcid.org/0000-0002-4774-5590, Fournier, Anna L, Hocqueloux, Laurent, Braun, Dominique L, Metzner, Karin J, Kouyos, Roger D, Raffi, François, Briant, Anaïs R, Martinez, Esteban, De Lazzari, Elisa, Negredo, Eugenia, Rijnders, Bart, Rokx, Casper, Günthard, Huldrych F, and Parienti, Jean-Jacques; https://orcid.org/0000-0002-4774-5590
Abstract: Background Dolutegravir monotherapy (DTG-m) results in virological failure (VF) in some people with human immunodeficiency virus (PWH). We sought to identify the independent factors associated with the risk of VF and to explore the effect size heterogeneity between subgroups of PWH enrolled in DTG-m trials. Methods We searched for randomized clinical trials (RCTs) evaluating DTG-m versus combined antiretroviral therapy (cART) among PWH virologically controlled for at least 6 months on cART. We performed an individual participant data meta-analysis of VF risk factors and quantified their explained heterogeneity in random-effect models. Definition of VF was a confirmed plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) >50 copies/mL by week 48. Results Among 416 PWH from 4 RCTs, DTG-m significantly increased the risk of VF (16 of 227 [7%] versus 0 of 189 for cART; risk difference 7%; 95% confidence interval [CI], 1%-2%; P = .02; I$^{2}$ = 51%). Among 272 participants exposed to DTG-m, VF were more likely in participants with the following: first cART initiated ≥90 days from HIV acute infection (adjusted hazard ratio [aHR], 5.16; 95% 95% CI, 1.60-16.65), CD4 T cells nadir <350/mm$^{3}$ (aHR, 12.10; 95% CI, 3.92-37.40), HIV RNA signal at baseline (aHR, 4.84; 95% CI, 3.68-6.38), and HIV-deoxyribonucleic acid (DNA) copy number at baseline ≥2.7 log/10$^{6}$ peripheral blood mononuclear cells (aHR, 3.81; 95% CI, 1.99-7.30). Among these independent risk factors, the largest effect size heterogeneity was found between HIV DNA subgroups (I$^{2}$ = 80.2%; P for interaction = .02). Conclusions Our study supports the importance of a large viral reservoir size for explaining DTG-m simplification strategy failure. Further studies are needed to link size and genetic diversity of the HIV-1 reservoir.
Published: 2022

30. Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial

Author: Speich, Benjamin; https://orcid.org/0000-0002-3301-8085, Chammartin, Frédérique, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Amico, Patrizia, Stoeckle, Marcel P, Eichenberger, Anna L, Hasse, Barbara; https://orcid.org/0000-0001-7196-3734, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Schuurmans, Macé M; https://orcid.org/0000-0001-5404-7566, Müller, Thomas F; https://orcid.org/0000-0003-2236-2312, Tamm, Michael, Audigé, Annette, Mueller, Nicolas J; https://orcid.org/0000-0002-1059-3191, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Koller, Michael T, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Briel, Matthias; https://orcid.org/0000-0002-2070-5230, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Bucher, Heiner C; https://orcid.org/0000-0002-0131-7873, et al, Schanz, Urs, Speich, Benjamin; https://orcid.org/0000-0002-3301-8085, Chammartin, Frédérique, Abela, Irene A; https://orcid.org/0000-0002-5566-8628, Amico, Patrizia, Stoeckle, Marcel P, Eichenberger, Anna L, Hasse, Barbara; https://orcid.org/0000-0001-7196-3734, Braun, Dominique L; https://orcid.org/0000-0003-4036-1030, Schuurmans, Macé M; https://orcid.org/0000-0001-5404-7566, Müller, Thomas F; https://orcid.org/0000-0003-2236-2312, Tamm, Michael, Audigé, Annette, Mueller, Nicolas J; https://orcid.org/0000-0002-1059-3191, Rauch, Andri; https://orcid.org/0000-0001-5297-6062, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Koller, Michael T, Trkola, Alexandra; https://orcid.org/0000-0003-1013-876X, Briel, Matthias; https://orcid.org/0000-0002-2070-5230, Kusejko, Katharina; https://orcid.org/0000-0002-4638-1940, Bucher, Heiner C; https://orcid.org/0000-0002-0131-7873, et al, and Schanz, Urs
Abstract: BACKGROUND: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. METHODS: Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2). RESULTS: A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI]: 88.4-95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2-97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8-93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4-93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2-71.9; 43/71) had titers above the cutoff level. CONCLUSIONS: In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.
Published: 2022

31. Quantifying and predicting ongoing Human Immunodeficiency Virus Type 1 (HIV-1) transmission dynamics in Switzerland using a distance-based clustering approach

Author: Labarile, Marco, Loosli, Tom, Zeeb, Marius, Kusejko, Katharina, Huber, Michael, Hirsch, Hans H, Perreau, Matthieu, Ramette, Alban, Yerly, Sabine, Cavassini, Matthias, Battegay, Manuel, Rauch, Andri, Calmy, Alexandra, Notter, Julia, Bernasconi, Enos, Fux, Christoph, Günthard, Huldrych F, Pasin, Chloé, and Kouyos, Roger D
Subjects: 610 Medizin und Gesundheit, 570 Biowissenschaften, Biologie
Abstract: BACKGROUND Despite effective prevention approaches, ongoing HIV-1 transmission remains a public health concern indicating a need for identifying its drivers. METHODS We combine a network-based clustering method using evolutionary distances between viral sequences with statistical learning approaches to investigate the dynamics of HIV-1 transmission in the Swiss HIV Cohort Study and to predict the drivers of ongoing transmission. RESULTS We find that only a minority of clusters and patients acquire links to new infections between 2007 and 2020. While the growth of clusters and the probability of individual patients acquiring new links in the transmission network was associated with epidemiological, behavioral and virological predictors, the strength of these associations decreased substantially when adjusting for network characteristics. Thus, these network characteristics can capture major heterogeneities beyond classical epidemiological parameters. When modeling the probability of a newly diagnosed patient being linked with future infections, we found that the best predictive performance (median AUCROC = 0.77) was achieved by models including characteristics of the network as predictors and that models excluding them performed substantially worse (median AUCROC = 0.54). CONCLUSIONS These results highlight the utility of molecular epidemiology-based network approaches for analysing and predicting ongoing HIV-1-transmission dynamics. This approach may serve for real-time prospective assessment of HIV-1-transmission.
Published: 2022
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32. HBV REPLICATION DURING TENOFOVIR THERAPY IS FREQUENT IN HIV/HBV-COINFECTION

Author: Hofmann, Eveline, Surial, Bernard, Boillat-Blanco, Noémie, Günthard, Huldrych F, Stöckle, Marcel, Bernasconi, Enos, Schmid, Patrick, Calmy, Alexandra, Suter-Riniker, Franziska, Rauch, Andri, Wandeler, Gilles, and Béguelin, Charles
Subjects: 360 Soziale Probleme, Sozialdienste, 610 Medizin und Gesundheit, 570 Biowissenschaften, Biologie
Abstract: In the Swiss HIV Cohort Study, 61/222 (27%) HIV-suppressed persons with chronic hepatitis B virus (HBV) infection had HBV replication after two years on tenofovir, of whom 77% were suppressed thereafter. Self-reported adherence to therapy and HBV viral load at tenofovir initiation were predictors of persistent replication.
Published: 2022
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33. Cohort-derived machine learning models for individual prediction of chronic kidney disease in people living with HIV: a prospective multicentre cohort study

Author: Roth, Jan A, Radevski, Gorjan, Marzolini, Catia, Rauch, Andri, Günthard, Huldrych F, Kouyos, Roger D, Fux, Christoph A, Scherrer, Alexandra U, Calmy, Alexandra, Cavassini, Matthias, Kahlert, Christian R, Bernasconi, Enos, Bogojeska, Jasmina, Battegay, Manuel, and University of Zurich
Subjects: 10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 610 Medicine & health
Abstract: BACKGROUND It is unclear whether data-driven machine learning models, which are trained on large epidemiological cohorts, may improve prediction of co-morbidities in people living with HIV. METHODS In this proof-of-concept study, we included people living with HIV of the prospective Swiss HIV Cohort Study with a first estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 after January 1, 2002. Our primary outcome was chronic kidney disease (CKD) ─ defined as confirmed decrease in eGFR ≤60 ml/min/1.73 m2 over three months apart. We split the cohort data into a training set (80%), validation set (10%), and test set (10%) ─ stratified for CKD status and follow-up length. RESULTS Of 12,761 eligible individuals (median baseline eGFR, 103 ml/min/1.73 m2), 1,192 (9%) developed a CKD after a median of eight years. We used 64 static and 502 time-changing variables: Across prediction horizons and algorithms and in contrast to expert-based standard models, most machine learning models achieved state-of-the-art predictive performances with areas under the receiver operating characteristic curve and precision recall curve ranging from 0.926 to 0.996 and from 0.631 to 0.956, respectively. CONCLUSIONS In people living with HIV, we observed state-of-the-art performances in forecasting individual CKD onsets with different machine learning algorithms.
Published: 2021
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34. Association of Incomplete Adherence to Antiretroviral Therapy With Cardiovascular Events and Mortality in Virologically Suppressed Persons With HIV: The Swiss HIV Cohort Study

Author: Castillo-Mancilla, Jose R, Cavassini, Matthias, Schneider Voirol, Marie Paule, Furrer, Hansjakob, Calmy, Alexandra, Battegay, Manuel, Scanferla, Giulia, Bernasconi, Enos, Günthard, Huldrych F, Glass, Tracy R, Anagnostopoulos, A, Battegay, M, Bernasconi, E, Böni, J, Braun, D L, Bucher, H C, Calmy, A, Cavassini, M, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Furrer, H, Fux, C A, Günthard, H F, Haerry, D, Hasse, B, Hirsch, H H, Hoffmann, M, Hösli, I, Huber, M, Kahlert, C R, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R D, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Marzolini, C, Metzner, K J, Müller, N, Nicca, D, Paioni, P, Pantaleo, G, Perreau, M, Rauch, A, Rudin, C, Scherrer, A U, Schmid, P, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Weber, R, Yerly, S, Swiss HIV Cohort Study, Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.
Subjects: 0301 basic medicine, medicine.medical_specialty, viral suppression, antiretroviral therapy, 610 Medicine & health, Disease, Major Articles, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, cardiovascular disease, Internal medicine, adherence, medicine, 030212 general & internal medicine, Myocardial infarction, Imputation (statistics), Stroke, ddc:615, business.industry, Proportional hazards model, Hazard ratio, Cardiovascular disease, medicine.disease, Viral suppression, 030112 virology, Antiretroviral therapy, Infectious Diseases, AcademicSubjects/MED00290, Oncology, Adherence, business, Cohort study
Abstract: BackgroundIncomplete antiretroviral therapy (ART) adherence, even if sufficient to maintain viral suppression, is associated with enhanced inflammation in persons with HIV (PWH). However, its clinical implications remain unknown.MethodsPWH enrolled in the Swiss HIV Cohort Study without a history of cardiovascular disease (CVD) who initiated ART between 2003 and 2018 and had viral suppression (ResultsA total of 6971 PWH (74% male) were included in the analysis (median age [interquartile range {IQR}], 39 [32–47] years). The median (IQR) follow-up was 8 (4–11) years, with 14 (8–23) adherence questionnaires collected per participant. In total, 205 (3%) participants experienced a CVD event, and 186 (3%) died a non-CVD-related death. In an adjusted competing risk model where missing data were imputed, missing ≥1 ART dose showed an increased, but not statistically significant, risk for CVD events (hazard ratio [HR], 1.23; 95% CI, 0.85–1.79; P = .28). Non-CVD-related mortality showed a statistically significantly increased risk with missing ≥1 ART dose (HR, 1.44; 95% CI, 1.00–2.07; P = .05) and missing ≥2 ART doses (HR, 2.21; 95% CI, 1.37–3.57; P = .001).ConclusionsIncomplete ART adherence was significantly associated with an increased risk for non-CVD-related mortality in PWH with virologic suppression. This highlights the potential role of nonadherence to ART as a driver of non-AIDS clinical outcomes.
Published: 2021
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35. Clinical outcomes of two-drug regimens vs. three-drug regimens in antiretroviral treatment-experienced people living with HIV

Author: Greenberg, Lauren, Ryom, Lene, Neesgaard, Bastian, Wandeler, Gilles, Staub, Therese, Gisinger, Martin, Skoll, Michael, Günthard, Huldrych F, et al, and University of Zurich
Subjects: 10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 570 Life sciences, biology, 610 Medicine & health
Published: 2021
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36. Predictors of virological failure and time to viral suppression of first line integrase inhibitor based antiretroviral treatment

Author: Pyngottu, Ashima, Scherrer, Alexandra U, Kouyos, Roger, Huber, Michael, Hirsch, Hans, Perreau, Matthieu, Yerly, Sabine, Calmy, Alexandra, Cavassini, Matthias, Stöckle, Marcel, Furrer, Hansjakob, Vernazza, Pietro, Bernasconi, Enos, Günthard, Huldrych F, Swiss HIV Cohort Study, Pyngottu, Ashima, Scherrer, Alexandra U, Kouyos, Roger, Huber, Michael, Hirsch, Hans, Perreau, Matthieu, Yerly, Sabine, Calmy, Alexandra, Cavassini, Matthias, Stöckle, Marcel, Furrer, Hansjakob, Vernazza, Pietro, Bernasconi, Enos, Günthard, Huldrych F, and Swiss HIV Cohort Study
Abstract: BACKGROUND Integrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of HIV-infection. We identified risk factors, including baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens. METHODS We studied time to treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study.We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS defining events and the type of InSTI.In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations. RESULTS We observed 121 virological failures during 18'447 person-years of follow-up. A baseline viral load ≥100'000 cps/mL (multivariable Hazard Ratio (mHR): 2.2, 95% CI: 1.3-3.6) and an AIDS defining event (mHR: 1.8, 95% CI: 1.1-3.0) were associated with treatment failure. CD4 counts between 200-500 cells/µL (mHR: 0.5, 95% CI: 0.3-0.8) and >500 cells/µL (mHR: 0.4, 95% CI: 0.2-0.7) were protective. Median [IQR] time to viral suppression was 50 [29,107] days. Time to suppression was shorter in lower viral load strata (mHR: 0.7, 95% CI: 0.6-0.8) and in dolutegravir-based therapy (mHR: 1.2, 95% CI: 1.0-1.4). Minor resistance mutations were found at baseline in 104/646 (16%) patients with no effect on treatment outcome. CONCLUSION Among drug-naïve HIV-infected individuals treated with InSTI-based regimens, factors associated with treatment failure, in particular high viral load and low CD4 counts remain similar to older treatments. Minor InSTI resistance mutations had no impact in this large observational cohort.
Published: 2021

37. Emergence of Human Immunodeficiency Virus-1 Drug Resistance During the 3-Month World Health Organization-Recommended Enhanced Adherence Counseling Period in the CART-1 Cohort Study

Author: Brown, Jennifer A; https://orcid.org/0000-0003-1874-6153, Mbunkah, Herbert A; https://orcid.org/0000-0002-4671-0281, Lejone, Thabo I; https://orcid.org/0000-0003-1724-1532, Ringera, Isaac, Cheleboi, Molisana, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, Tschumi, Nadine; https://orcid.org/0000-0002-7303-9542, Brown, Jennifer A; https://orcid.org/0000-0003-1874-6153, Mbunkah, Herbert A; https://orcid.org/0000-0002-4671-0281, Lejone, Thabo I; https://orcid.org/0000-0003-1724-1532, Ringera, Isaac, Cheleboi, Molisana, Klimkait, Thomas; https://orcid.org/0000-0003-4945-6511, Metzner, Karin J; https://orcid.org/0000-0003-4862-1503, Günthard, Huldrych F; https://orcid.org/0000-0002-1142-6723, Labhardt, Niklaus D; https://orcid.org/0000-0003-3599-1791, Kouyos, Roger D; https://orcid.org/0000-0002-9220-8348, and Tschumi, Nadine; https://orcid.org/0000-0002-7303-9542
Abstract: Background In resource-limited settings, the World Health Organization recommends enhanced adherence counseling (EAC) for individuals with an unsuppressed human immunodeficiency virus (HIV)-1 viral load (VL) and to remeasure VL after 3 months to avoid unnecessary regimen switches. In cases in which this follow-up VL remains unsuppressed, a regimen switch is indicated. We aimed to assess levels of HIV-1 drug resistance before and after the EAC period among people with ongoing viremia (≥80 c/mL) after EAC. Methods We included adult participants of the CART-1 cohort study conducted in Lesotho who had a VL ≥80 c/mL after EAC. Paired plasma samples (before and after EAC) were analyzed by next-generation sequencing. We assessed the prevalence of resistance-associated mutations and viral susceptibility scores to each participant's antiretroviral therapy (ART) regimen (range, 0-3; 3 indicates complete susceptibility). Results Among 93 participants taking nonnucleoside reverse-transcriptase inhibitor-based ART with an initial VL ≥1000 copies/mL who received a follow-up VL test after EAC, 76 still had a VL ≥80 copies/mL after EAC, and paired samples were available for 57 of 76. The number of individuals without full susceptibility to any drug in their regimen increased from 31 of 57 (54.4%) before to 36 of 57 (63.2%) after EAC. Median susceptibility scores dropped from 0.5 (interquartile range [IQR] = 0.25-) to 0.25 (IQR = 0.25-1) during the EAC period (P = .16). Conclusions Despite high levels of resistance before EAC, we observed a slight decline in susceptibility scores after EAC. The risk of further accumulation of resistance during EAC has to be balanced against the benefit of avoiding unnecessary switches in those with spontaneous resuppression after EAC.
Published: 2021

38. Self-reported neurocognitive impairment in people living with HIV: Characterizing clusters of patients with similar changes in self-reported neurocognitive impairment 2013-2017 in the Swiss HIV Cohort Study

Author: Kusejko, Katharina, Salazar Vizcaya, Luisa, Braun, Dominique L, Tarr, Philip E, Bernasconi, Enos, Doco-Lecompte, Thanh, Cavassini, Matthias, Schmid, Patrick, Du Pasquier, Renaud, Hauser, Christoph, Günthard, Huldrych F, and Kouyos, Roger D
Subjects: 610 Medicine & health
Abstract: INTRODUCTION Self-reported neurocognitive impairment (srni) in people living with human immunodeficiency virus-1 (HIV-1) infection are frequent. We use longitudinal information on srni in the Swiss HIV Cohort Study (SHCS) to identify and characterize groups of patients with persisting srni over time. METHODS We included all SHCS patients who were assessed for srni during at least 5 visits spanning at least 2.5 years in 2013-2017. We first compared patients with srni to those without srni over the whole study period. Second, we used a hierarchical cluster algorithm to identify groups of patients with similar changes of srni over time. In both analyses, we studied clinical and demographic factors potentially influencing srni. RESULTS In total, 79'683 questionnaires of 11'029 patients contained information about srni, and 8'545/11'029 (77.5%) patients had longitudinal information. The overall percentage of patients with srni decreased from 19.6% in 2013 to 10.7% in 2017. Compared to patients in the cluster with low-level srni over time, patients in the cluster with high-level persisting srni had more often a prior opportunistic infection of the central nervous system (CNS) (OR=3.7, p
Published: 2020
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39. Clusters of sexual behaviour in HIV-positive men who have sex with men reveal highly dissimilar time trends

Author: Salazar Vizcaya, Luisa Paola, Kusejko, Katharina, Schmidt, Axel J, Carrillo-Montoya, Germán, Nicca, Dunja, Wandeler, Gilles, Braun, Dominique L, Fehr, Jan, Darling, Katharine E A, Bernasconi, Enos, Schmid, Patrick, Günthard, Huldrych F, Kouyos, Roger D, Rauch, Andri, University of Zurich, and Salazar-Vizcaya, Luisa
Subjects: 10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 610 Medicine & health, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 2725 Infectious Diseases, 2726 Microbiology (medical)
Abstract: BACKGROUND Separately addressing specific groups of people who share patterns of behavioural change might increase the impact of behavioural interventions to prevent transmission of sexually transmitted infections. We propose a method based on machine learning to assist the identification of such groups among men who have sex with men (MSM). METHODS By means of unsupervised learning, we inferred "behavioural clusters" based on the recognition of similarities and differences in longitudinal patterns of condomless anal intercourse with non-steady partners (nsCAI) in the Swiss HIV cohort study over the last 18 years. We then used supervised learning to investigate whether sociodemographic variables could predict cluster membership. RESULTS We identified four behavioural clusters. The largest behavioural cluster (Cluster 1) contained 53% of the study population and displayed the most stable behaviour. Cluster 3 (17% of the study population) displayed consistently increasing nsCAI. Sociodemographic variables were predictive for both of these clusters. The other two clusters displayed more drastic changes: nsCAI frequency in Cluster 2 (20% of the study population) was initially similar to that in Cluster 3, but accelerated in 2010. Cluster 4 (10% of the study population) had significantly lower estimates of nsCAI than all other clusters until 2017, when it increased drastically, reaching 85% by the end of the study period. CONCLUSIONS We identified highly dissimilar behavioural patterns across behavioural clusters, including drastic, atypical changes. These patterns suggest that the overall increase in the frequency of nsCAI is largely attributable to two clusters, accounting for a third of the population.
Published: 2020
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40. Telomere Length, Traditional Risk Factors, HIV-related Factors and Coronary Artery Disease Events in Swiss Persons Living with HIV

Author: Engel, Tanja, Raffenberg, Marieke, Schoepf, Isabella C, Kootstra, Neeltje A, Reiss, Peter, Thorball, Christian W, Hasse, Barbara, Hirzel, Cédric, Wissel, Kerstin, Roth, Jan A, Bernasconi, Enos, Darling, Katharine E A, Calmy, Alexandra, Fellay, Jacques, Kouyos, Roger D, Günthard, Huldrych F, Ledergerber, Bruno, Tarr, Philip E, and University of Zurich
Subjects: 10028 Institute of Medical Virology, 10234 Clinic for Infectious Diseases, 610 Medicine & health
Abstract: BACKGROUND Leukocyte telomere length (TL) shortens with age and is associated with coronary artery disease (CAD) events in the general population. Persons living with HIV (PLWH) may have accelerated atherosclerosis and shorter TL than the general population. It is unknown whether TL is associated with CAD in PLWH. METHODS We measured TL by quantitative PCR in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 01.01.2000-31.12.2017. We matched 1-3 PLWH controls without CAD events on sex, age, and observation time. We obtained univariable and multivariable odds ratios (OR) for CAD from conditional logistic regression analyses. RESULTS We included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9-13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR=0.56 (95% confidence interval, 0.35-0.91) and OR=0.54 (0.31-0.96). Multivariable OR for current smoking was 1.93 (1.27-2.92), dyslipidemia OR=1.92 (1.41-2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR=1.82 (1.27-2.59), OR=2.02 (1.34-3.04), OR=3.42 (2.14-5.45), and OR=1.66 (1.00-2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use. CONCLUSION In PLWH, TL measured >9 years before, is independently associated with CAD events after adjusting for multiple traditional and HIV-related factors.
Published: 2020
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41. Clusters of sexual behaviour in HIV-positive men who have sex with men reveal highly dissimilar time trends

Author: Salazar-Vizcaya, Luisa, Kusejko, Katharina, Schmidt, Axel J, Carrillo-Montoya, Germán, Nicca, Dunja, Wandeler, Gilles, Braun, Dominique L, Fehr, Jan, Darling, Katharine E A, Bernasconi, Enos, Schmid, Patrick, Günthard, Huldrych F, Kouyos, Roger D, Rauch, Andri, Salazar-Vizcaya, Luisa, Kusejko, Katharina, Schmidt, Axel J, Carrillo-Montoya, Germán, Nicca, Dunja, Wandeler, Gilles, Braun, Dominique L, Fehr, Jan, Darling, Katharine E A, Bernasconi, Enos, Schmid, Patrick, Günthard, Huldrych F, Kouyos, Roger D, and Rauch, Andri
Abstract: BACKGROUND Separately addressing specific groups of people who share patterns of behavioural change might increase the impact of behavioural interventions to prevent transmission of sexually transmitted infections. We propose a method based on machine learning to assist the identification of such groups among men who have sex with men (MSM). METHODS By means of unsupervised learning, we inferred "behavioural clusters" based on the recognition of similarities and differences in longitudinal patterns of condomless anal intercourse with non-steady partners (nsCAI) in the Swiss HIV cohort study over the last 18 years. We then used supervised learning to investigate whether sociodemographic variables could predict cluster membership. RESULTS We identified four behavioural clusters. The largest behavioural cluster (Cluster 1) contained 53% of the study population and displayed the most stable behaviour. Cluster 3 (17% of the study population) displayed consistently increasing nsCAI. Sociodemographic variables were predictive for both of these clusters. The other two clusters displayed more drastic changes: nsCAI frequency in Cluster 2 (20% of the study population) was initially similar to that in Cluster 3, but accelerated in 2010. Cluster 4 (10% of the study population) had significantly lower estimates of nsCAI than all other clusters until 2017, when it increased drastically, reaching 85% by the end of the study period. CONCLUSIONS We identified highly dissimilar behavioural patterns across behavioural clusters, including drastic, atypical changes. These patterns suggest that the overall increase in the frequency of nsCAI is largely attributable to two clusters, accounting for a third of the population.
Published: 2020

42. High Number of Potential Transmitters Revealed in a Population-based Systematic Hepatitis C Virus RNA Screening Among Human Immunodeficiency Virus-infected Men Who Have Sex With Men

Author: Braun, Dominique L, Hampel, Benjamin, Martin, Eileen, Kouyos, Roger, Kusejko, Katharina, Grube, Christina, Flepp, Markus, Stöckle, Marcel, Conen, Anna, Béguelin, Charles Antoine, Schmid, Patrick, Delaloye, Julie, Rougemont, Mathieu, Bernasconi, Enos, Rauch, Andri, Günthard, Huldrych F, Böni, Jürg, and Fehr, Jan S
Subjects: virus diseases, 610 Medicine & health, digestive system diseases
Abstract: Background The proportion of undiagnosed hepatitis C virus (HCV) infections in high-risk populations, such as human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) is unclear. Identification of potential HCV transmitters is important to reach World Health Organization HCV elimination targets. Methods Between October 2015 and May 2016, we performed a systematic HCV RNA-based screening among HIV-infected MSM participating in the Swiss HIV Cohort Study (SHCS). HCV antibodies were measured from all HCV RNA-positive samples. Results Of 4257 MSM recorded in the SHCS database, we screened 3722 (87%) by HCV polymerase chain reaction, and 177 (4.8%) harbored a replicating HCV infection. We identified 24 individuals (14%) with incident HCV infection; one-third of them had a negative HCV antibody result at the time of HCV RNA positivity. In a multivariable model, elevated liver enzyme values (odds ratio, 14.52; 95% confidence interval, 9.92-21.26), unprotected sex with occasional partners (2.01; 1.36-2.98), intravenous drug use (7.13; 4.36-11.64), noninjectable drug use (1.94; 1.3-2.88), and previous syphilis diagnosis (2.56; 1.74-3.76) were associated with HCV RNA positivity. Conclusions A systematic HCV RNA-based screening among HIV-infected MSM revealed a high number of potential transmitters. A substantial subpopulation of MSM had incident infection, one-third of whom had a negative HCV antibody test result at the time of the HCV RNA positivity. These data reveal that one-time RNA testing of a high-risk population for HCV RNA might identify more infected persons than routine testing for HCV antibodies and liver enzymes.
Published: 2019
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43. Changing trends in international versus domestic HCV transmission in HIV-positive MSM: A perspective for the DAA scale-up era

Author: Salazar-Vizcaya, Luisa, Kouyos, Roger D, Metzner, Karin J, Caraballo Cortes, Kamila, Böni, Jürg, Shah, Cyril, Fehr, Jan, Braun, Dominique L, Bernasconi, Enos, Mbunkah, Herbert A, Hoffmann, Matthias, Labhardt, Niklaus, Cavassini, Matthias, Rougemont, Mathieu, Günthard, Huldrych F, Keiser, Olivia, and Rauch, Andri
Subjects: virus diseases, 610 Medicine & health, ddc:613
Abstract: Background Scale-up of direct-acting antiviral(DAA) therapy is expected to abate HCV incidence among HIV-positive men-who-have-sex-with-men(MSM). Treatment programs in neighbouring countries may influence each other's outcomes through international transmission. We aimed at classifying HCV infections in HIV-positive MSM as either domestically or internationally acquired, and at estimating how this classification changed over time. Methods HCV subtype 1a (the most frequent subtype among MSM) genomes from 99 persons enrolled in the Swiss-HIV-Cohort-Study(SHCS) and diagnosed with replicating HCV infections between 1999 and 2016, were sequenced. Sixty-six of these sequences were from MSM. We inferred maximum-likelihood phylogenetic-trees and time-trees containing a fragment of the NS5B region of these and other 374 circulating strains retrieved from national and international databases. We inferred transmission clusters from these trees and used the country composition of such clusters to attribute infections to domestic or international transmission. Results Fifty to 80% of HCV transmissions were classified as domestic depending on the classification criterion. Between 2000 and 2007, the fraction attributable to domestic transmission was 54%[range:0%-75%]. It increased to 85%[range:67%-100%] between 2008 and 2016. Conclusions International and domestic transmission have played major roles in the epidemic. While international transmission persists, local transmission has established as the main source of infections.
Published: 2019
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44. A systematic phylogenetic approach to study the interaction of HIV-1 with coinfections, non-communicable and opportunistic diseases

Author: Kusejko, Katharina, Bachmann, Nadine, Chaudron, Sandra E, Nguyen, Huyen, Braun, Dominique L, Hampel, Benjamin, Battegay, Manuel, Bernasconi, Enos, Calmy, Alexandra, Cavassini, Matthias, Hoffmann, Matthias, Böni, Jürg, Yerly, Sabine, Klimkait, Thomas, Perreau, Matthieu, Rauch, Andri, Günthard, Huldrych F, and Kouyos, Roger D
Subjects: 610 Medicine & health
Abstract: To systematically test whether coinfections spread along the HIV-1 transmission network and whether similarities of HIV-1 genomes predict AIDS-defining illnesses and comorbidities, we analyzed the distribution of these variables on the HIV-phylogeny of the densely sampled Swiss HIV Cohort Study. By combining different statistical methods, we could detect, quantify and explain the clustering of diseases: Infectious conditions such as hepatitis C, but also Kaposi's sarcoma, clustered significantly, suggesting transmission of these infections along the HIV-1 transmission network. The clustering of patients with neurocognitive complaints, however, could not be completely explained by the clustering of patients with similar demographic risk factors, which suggests a potential impact of viral genetics. In summary, the consistent and robust signal for infectious conditions highlights the strong interaction of HIV-1 and other infections and shows the potential of combining phylogenetic methods to identify disease traits that are likely to be related to virus genetic factors.
Published: 2019
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45. Human Immunodeficiency Virus Drug Resistance : 2018 Recommendations of the International Antiviral Society-USA Panel

Author: Günthard, Huldrych F., Calvez, Vincent, Paredes, Roger, Pillay, Deenan, Shafer, Robert W., Wensing, Annemarie M., Jacobsen, Donna M., Richman, Douglas D., Günthard, Huldrych F., Calvez, Vincent, Paredes, Roger, Pillay, Deenan, Shafer, Robert W., Wensing, Annemarie M., Jacobsen, Donna M., and Richman, Douglas D.
Published: 2019

46. Reply to Ambrosioni et al

Author: Günthard, Huldrych F., Calvez, Vincent, Paredes, Roger, Pillay, Deenan, Shafer, Robert W., Wensing, Annemarie M., Jacobsen, Donna M., Richman, Douglas D., Günthard, Huldrych F., Calvez, Vincent, Paredes, Roger, Pillay, Deenan, Shafer, Robert W., Wensing, Annemarie M., Jacobsen, Donna M., and Richman, Douglas D.
Published: 2019

47. Corrigendum to: Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients

Author: Olearo, Flaminia; https://orcid.org/0000-0002-5118-9523, Nguyen, Huyen, Bonnet, Fabrice, Yerly, Sabine, Wandeler, Gilles, Stoeckle, Marcel, Cavassini, Matthias, Scherrer, Alexandra, Costagliola, Dominique, Schmid, Patrick, Günthard, Huldrych F, Bernasconi, Enos, Boeni, Jürg, D'arminio Monforte, Antonella, Zazzi, Maurizio, Rossetti, Barbara, Neau, Didier, Bellecave, Pantxika, Rijnders, Bart, Reiss, Peter, Wit, Ferdinand, Kouyos, Roger, Calmy, Alexandra, Olearo, Flaminia; https://orcid.org/0000-0002-5118-9523, Nguyen, Huyen, Bonnet, Fabrice, Yerly, Sabine, Wandeler, Gilles, Stoeckle, Marcel, Cavassini, Matthias, Scherrer, Alexandra, Costagliola, Dominique, Schmid, Patrick, Günthard, Huldrych F, Bernasconi, Enos, Boeni, Jürg, D'arminio Monforte, Antonella, Zazzi, Maurizio, Rossetti, Barbara, Neau, Didier, Bellecave, Pantxika, Rijnders, Bart, Reiss, Peter, Wit, Ferdinand, Kouyos, Roger, and Calmy, Alexandra
Abstract: [This corrects the article DOI: 10.1093/ofid/ofz330.][This corrects the article DOI: 10.1093/ofid/ofz330.].
Published: 2019

48. Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients

Author: Olearo, Flaminia; https://orcid.org/0000-0002-5118-9523, Nguyen, Huyen, Bonnet, Fabrice, Yerly, Sabine, Wandeler, Gilles, Stoeckle, Marcel, Cavassini, Matthias, Scherrer, Alexandra, Costagiola, Dominique, Schmid, Patrick, Günthard, Huldrych F, Bernasconi, Enos, Boeni, Jürg, D'arminio Monforte, Antonella, Zazzi, Maurizio, Rossetti, Barbara, Neau, Didier, Bellecave, Pantxika, Rijnders, Bart, Reiss, Peter, Wit, Ferdinand, Kouyos, Roger, Calmy, Alexandra, Olearo, Flaminia; https://orcid.org/0000-0002-5118-9523, Nguyen, Huyen, Bonnet, Fabrice, Yerly, Sabine, Wandeler, Gilles, Stoeckle, Marcel, Cavassini, Matthias, Scherrer, Alexandra, Costagiola, Dominique, Schmid, Patrick, Günthard, Huldrych F, Bernasconi, Enos, Boeni, Jürg, D'arminio Monforte, Antonella, Zazzi, Maurizio, Rossetti, Barbara, Neau, Didier, Bellecave, Pantxika, Rijnders, Bart, Reiss, Peter, Wit, Ferdinand, Kouyos, Roger, and Calmy, Alexandra
Abstract: Objective The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated. Method This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population. Results We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154-441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2-79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4-21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35-4.59 and HR 1.66; 95% CI, 0.81-3.43, respectively). Conclusions In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.
Published: 2019

49. Changing Trends in International Versus Domestic HCV Transmission in HIV-Positive Men Who Have Sex With Men: A Perspective for the Direct-Acting Antiviral Scale-Up Era

Author: Salazar-Vizcaya, Luisa, Kouyos, Roger D, Metzner, Karin J, Caraballo Cortes, Kamila, Böni, Jürg, Shah, Cyril, Fehr, Jan, Braun, Dominique L, Bernasconi, Enos, Mbunkah, Herbert A, Hoffmann, Matthias, Labhardt, Niklaus, Cavassini, Matthias, Rougemont, Mathieu, Günthard, Huldrych F, Keiser, Olivia, Rauch, Andri, Swiss HIV Cohort Study, Salazar-Vizcaya, Luisa, Kouyos, Roger D, Metzner, Karin J, Caraballo Cortes, Kamila, Böni, Jürg, Shah, Cyril, Fehr, Jan, Braun, Dominique L, Bernasconi, Enos, Mbunkah, Herbert A, Hoffmann, Matthias, Labhardt, Niklaus, Cavassini, Matthias, Rougemont, Mathieu, Günthard, Huldrych F, Keiser, Olivia, Rauch, Andri, and Swiss HIV Cohort Study
Abstract: BACKGROUND Scale-up of direct-acting antiviral therapy is expected to abate hepatitis C virus (HCV) incidence among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). International transmission could influence this process. We classified HCV infections in HIV-positive MSM as either domestically or internationally acquired, and estimated how this classification changed over time. METHODS HCV subtype 1a (the most frequent subtype among MSM) genomes from 99 persons enrolled in the Swiss HIV Cohort Study and diagnosed with replicating HCV infections, were sequenced. Sixty-six of these sequences were from MSM. We inferred maximum-likelihood phylogenetic trees and time trees containing a fragment of the NS5B region of these and 374 circulating strains. We inferred transmission clusters from these trees and used the country composition of such clusters to attribute infections to domestic or international transmission. RESULTS Of HCV transmissions, 50% to 80% were classified as domestic depending on the classification criterion. Between 2000 and 2007, the fraction attributable to domestic transmission was 54% (range 0-75%). It increased to 85% (range 67%-100%) between 2008 and 2016. CONCLUSIONS International and domestic transmission have played major roles in this epidemic. While international transmission persists, local transmission has established as the main source of infections.
Published: 2019

50. Human Immunodeficiency Virus Drug Resistance: 2018 Recommendations of the International Antiviral Society-USA Panel

Author: Günthard, Huldrych F, Calvez, Vincent, Paredes, Roger, Pillay, Deenan, Shafer, Robert W, Wensing, Annemarie M, Jacobsen, Donna M, Richman, Douglas D, Günthard, Huldrych F, Calvez, Vincent, Paredes, Roger, Pillay, Deenan, Shafer, Robert W, Wensing, Annemarie M, Jacobsen, Donna M, and Richman, Douglas D
Abstract: Background Contemporary antiretroviral therapies (ART) and management strategies have diminished both human immunodeficiency virus (HIV) treatment failure and the acquired resistance to drugs in resource-rich regions, but transmission of drug-resistant viruses has not similarly decreased. In low- and middle-income regions, ART roll-out has improved outcomes, but has resulted in increasing acquired and transmitted resistances. Our objective was to review resistance to ART drugs and methods to detect it, and to provide updated recommendations for testing and monitoring for drug resistance in HIV-infected individuals. Methods A volunteer panel of experts appointed by the International Antiviral (formerly AIDS) Society-USA reviewed relevant peer-reviewed data that were published or presented at scientific conferences. Recommendations were rated according to the strength of the recommendation and quality of the evidence, and reached by full panel consensus. Results Resistance testing remains a cornerstone of ART. It is recommended in newly-diagnosed individuals and in patients in whom ART has failed. Testing for transmitted integrase strand-transfer inhibitor resistance is currently not recommended, but this may change as more resistance emerges with widespread use. Sanger-based and next-generation sequencing approaches are each suited for genotypic testing. Testing for minority variants harboring drug resistance may only be considered if treatments depend on a first-generation nonnucleoside analogue reverse transcriptase inhibitor. Different HIV-1 subtypes do not need special considerations regarding resistance testing. Conclusions Testing for HIV drug resistance in drug-naive individuals and in patients in whom antiretroviral drugs are failing, and the appreciation of the role of testing, are crucial to the prevention and management of failure of ART.
Published: 2019

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