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1. Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand

Author

Goetghebuer T, Hainaut M, Van der Kelen E, Delforge M, Warszawski J, Le Chenadec J, Ramos E, Dialla O, Wack T, Laurent C, Selmi L, Leymarie I, Benali F, Brossard M, Boufassa L, Floch-Tudal C, Firtion G, Hau I, Chace A, Bolot P, Blanche S, Granier M, Labrune P, Lachassine E, Dollfus C, Levine M, Fourcade C, Heller-Roussin B, Runel-Belliard C, Tricoire J, Monpoux F, Chirouze C, Reliquet V, Brouard J, Kebaili K, Fialaire P, Lalande M, Mazingue F, Partisani M, Koenigs C, Schultze-Strasser S, Baumann U, Niehues T, Neubert J, Kobbe R, Feiterna-Sperling C, Buchholz B, Notheis G, Spoulou V, Tovo P, Galli L, Chiappini E, Patrizia O, Larovere D, Ruggeri M, Faldella G, Baldi F, Badolato R, Montagnani C, Venturini E, Lisi C, Di Biagio A, Taramasso L, Giacomet V, Erba P, Esposito S, Lipreri R, Salvini F, Tagliabue C, Cellini M, Bruzzese E, Lo Vecchio A, Rampon O, Dona D, Romano A, Dodi I, Maccabruni A, Consolini R, Bernardi S, Genovese O, Olmeo P, Cristiano L, Mazza A, Garazzino S, Pellegatta A, Pajkrt D, Scherpbier H, Weijsenfeld A, van der Plas A, Jurriaans S, Back N, Zaaijer H, Berkhout B, Cornelissen M, Schinkel C, Wolthers K, Fraaij P, van Rossum A, van der Knaap L, Visser E, Boucher C, Koopmans M, van Kampen J, Pas S, Henriet S, de Flier M, van Aerde K, Strik-Albers R, Rahamat-Langendoen J, Stelma F, Scholvinck E, de Groot-de Jonge H, Niesters H, van Leer-Buter C, Knoester M, Bont L, Geelen S, Wolfs T, Nauta N, Ang C, van Houdt R, Pettersson A, Vandenbroucke-Grauls C, Reiss P, Bezemer D, van Sighem A, Smit C, Wit F, Boender T, Zaheri S, Hillebregt M, de Jong A, Bergsma D, Grivell S, Jansen A, Raethke M, Meijering R, 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, Schoorl M, Timmerman A, Tuijn E, Veenenberg L, van der Vliet S, Wisse A, Woudstra T, Tuk B, Marczynska M, Oldakowska A, Popielska J, Coupland U, Doroba M, Marques L, Teixeira C, Fernandes A, Prata F, Ene L, Gingaras C, Radoi R, Okhonskaia L, Voronin E, Miloenko M, Labutina S, Soler-Palacin P, Antoinette Frick M, Perez-Hoyos S, Mur A, Lopez N, Mendez M, Mayol L, Vallmanya T, Calavia O, Garcia L, Coll M, Pineda V, Rius N, Rovira N, Duenas J, Fortuny C, Noguera-Julian A, Jose Mellado M, Escosa L, Garcia Hortelano M, Sainz T, Isabel Gonzalez-Tome M, Rojo P, Blazquez D, Tomas Ramos J, Prieto L, Guillen S, Luisa Navarro M, Saavedra J, Santos M, Angeles Munoz M, Ruiz B, Fernandez Mc Phee C, Jimenez de Ory S, Alvarez S, Angel Roa M, Beceiro J, Martinez J, Badillo K, Apilanez M, Pocheville I, Garrote E, Colino E, Gomez Sirvent J, Garzon M, Roman V, Montesdeoca A, Mateo M, Jose Munoz M, Angulo R, Neth O, Falcon L, Terol P, Luis Santos J, Moreno D, Lendinez F, Grande A, Jose Romero F, Perez C, Lillo M, Losada B, Herranz M, Bustillo M, Guerrero C, Collado P, Antonio Couceiro J, Perez A, Isabel Piqueras A, Breton R, Segarra I, Gavilan C, Jareno E, Montesinos E, Dapena M, Alvarez C, Gloria Andres A, Marugan V, Ochoa C, Alfayate S, Isabel Menasalvas A, de Miguel E, Naver L, Soeria-Atmadja S, Hagas V, Aebi-Popp K, Asner S, Aubert V, Battegay M, Baumann M, Bernasconi E, Boni J, Brazzola P, Bucher H, Calmy A, Cavassini M, Ciuffi A, Duppenthaler A, Dollenmaier G, Egger M, Elzi L, Fehr J, Fellay J, Francini K, Furrer H, Fux C, Grawe C, Gunthard H, Haerry D, Hasse B, Hirsch H, Hoffmann M, Hosli I, Kahlert C, Kaiser L, Keiser O, Klimkait T, Kovari H, Kouyos R, Ledergerber B, Martinetti G, de Tejada M, Metzner K, Muller, Nicca D, Paioni P, Pantaleo G, Polli C, Posfay-Barbe K, Rauch A, Rudin C, Schmid P, Scherrer A, Speck R, Tarr P, Lecompte T, Trkola A, Vernazza P, Wagner N, Wandeler G, Weber R, Wyler C, Yerly S, Techakunakorn P, Prachanukroh C, Hansudewechakul R, Wanchaitanawong V, Theansavettrakul S, Nanta S, Ngampiyaskul C, Phanomcheong S, Hongsiriwon S, Karnchanamayul W, Chacheongsao B, Kwanchaipanich R, Kanjanavanit S, Prapinklao S, Kamonpakorn N, Nantarukchaikul M, Adulyadej B, Layangool P, Mekmullica J, Lucksanapisitkul P, Watanayothin S, Lertpienthum N, Warachit B, Hanpinitsak S, Potchalongsin S, Thanasiri P, Krikajornkitti S, Attavinijtrakarn P, Srirojana S, Bunjongpak S, Puangsombat A, Na-Rajsima S, Ananpatharachai P, Akarathum N, Phuket V, Lawtongkum W, Kheunjan P, Suriyaboon T, Saipanya A, Than-in-at K, Jaisieng N, Suaysod R, Chailoet S, Naratee N, Kawilapat S, Kaleeva T, Baryshnikova Y, Soloha S, Bashkatova N, Raus I, Glutshenko O, Ruban Z, Prymak N, Kiseleva G, Bailey H, Lyall H, Butler K, Doerholt K, Foster C, Klein N, Menson E, Riordan A, Shingadia D, Tudor-Williams G, Tookey P, Welch S, Collins I, Cook C, Dobson D, Fairbrother K, Gibb D, Judd A, Harper L, Parrott F, Tostevin A, Van Looy N, Walsh A, Scott S, Vaughan Y, Laycock N, Bernatoniene J, Finn A, Hutchison L, Sharpe G, Williams A, Lyall E, Seery P, Lewis P, Miles K, Subramaniam B, Hutchinson L, Ward P, Sloper K, Gopal G, Doherty C, Hague R, Price V, Bamford A, Bundy H, Clapson M, Flynn J, Novelli V, Ainsley-Walker P, Tovey P, Gurtin D, Garside J, Fall A, Porter D, Segal S, Ball C, Hawkins S, Chetcuti P, Dowie M, Bandi S, McCabe A, Eisenhut M, Handforth J, Roy P, Flood T, Pickering A, Liebeschuetz S, Kavanagh C, Murphy C, Rowson K, Tan T, Daniels J, Lees Y, Kerr E, Thompson F, Le Provost M, Cliffe L, Smyth A, Stafford S, Freeman A, Reddy T, Fidler K, Christie S, Gordon A, Rogahn D, Harris S, Collinson A, Jones L, Offerman B, Van Someren V, Benson C, Riddell A, O'Connor R, Brown N, Ibberson L, Shackley F, Faust S, Hancock J, Donaghy S, Prime K, Sharland M, Storey S, Gorman S, Monrose C, Walters S, Cross R, Broomhall J, Scott D, Stroobant J, Bridgwood A, McMaster P, Evans J, Gardiner T, Jones R, Gardiner K, European Pregnancy Paediat HIV Coh, Stichting HIV Monitoring, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Department of Sciences for Woman and Child's Health, Florence University, Dipartimento di Pediatria, Azienda Ospedaliera di Padova, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pediatrics, and Virology

Subjects
Male, 0301 basic medicine, Time Factors, HIV, antiretroviral therapy, children, second-line, switch, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Drug Resistance, INFANTS, HIV Infections, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Interquartile range, Antiretroviral Therapy, Highly Active, ADOLESCENTS, Cumulative incidence, Viral, Treatment Failure, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, Antiretroviral therapy, Children, Second-line, Switch, Age Factors, Anti-HIV Agents, Child, Preschool, Drug Resistance, Viral, Drug Substitution, Europe, Female, Humans, Infant, Reverse Transcriptase Inhibitors, Thailand, Viral Load, Reverse-transcriptase inhibitor, Immunosuppression, OPEN-LABEL, VIROLOGICAL FAILURE, 3. Good health, Infectious Diseases, Viral load, medicine.drug, Microbiology (medical), medicine.medical_specialty, Efavirenz, Nevirapine, SCALE-UP, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Highly Active, Preschool, business.industry, HIV-1 DRUG-RESISTANCE, ADULTS, 030112 virology, RANDOMIZED-TRIAL, Regimen, INFECTED CHILDREN, VIRAL LOAD, chemistry, business
Abstract

Background. Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand.Methods. Children aged = 2 nucleoside reverse transcriptase inhibitors p[NRTIs] plus nonnucleoside reverse transcriptase inhibitor p[NNRTI] or boosted protease inhibitor p[PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of >= 1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks.Results. Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch.Conclusions. One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch.

Published
2017

2. Guidelines

Author

Fehr, Jan, Nicca, D, Langewitz, W, Haerry, D, and University of Zurich

Subjects
610 Medicine & health, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI)
Published
2018
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3. Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study: Changes in Treatment Uptake and Outcomes Between 1991 and 2013

Author

Wandeler, G., Schlauri, M., Jaquier, M.E., Rohrbach, J., Metzner, K.J., Fehr, J., Ambrosioni, J., Cavassini, M., Stöckle, M., Schmid, P., Bernasconi, E., Keiser, O., Salazar-Vizcaya, L., Furrer, H., Rauch, A., Aubert, V., Battegay, M., Böni, J., Bucher, H.C., Burton-Jeangros, C., Calmy, A., Dollenmaier, G., Egger, M., Elzi, L., Fellay, J., Fux, C.A., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., and Swiss HIV Cohort Study

Subjects
medicine.medical_specialty, Hepatitis C virus, 610 Medicine & health, treatment outcomes, medicine.disease_cause, Major Articles, Men who have sex with men, 360 Social problems & social services, Internal medicine, Medicine, Seroconversion, business.industry, virus diseases, Hepatitis C, medicine.disease, digestive system diseases, Confidence interval, 3. Good health, treatment uptake, Infectious Diseases, Oncology, acute HCV, Cohort, Immunology, 570 Life sciences, biology, business, Viral load, Cohort study
Abstract

In this large cohort of HIV-infected patients with an incident HCV infection, treatment uptake and outcomes improved in recent years. As a consequence, the proportion of patients with a detectable HCV viral load decreased significantly with time., Background. The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent. Methods. We included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up. Results. Of 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (P < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (P < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (P < .001). An SVR was achieved in 78% and 29% (P = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58–0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16–0.35) in the other group (P < .001). Conclusions. In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV.

Published
2015

4. The interplay between host genetic variation, viral replication and microbial translocation in untreated HIV-infected individuals

Author

Perkins, Molly R., Bartha, Istvan, Timmer, J. Katherina, Liebner, Julia C., Wollinsky, David, Günthard, Huldrych F., Hauser, Christoph, Bernasconi, Enos, Hoffmann, Matthias, Calmy, Alexandra, Battegay, Manuel, Telenti, Amalio, Douek, Daniel C., Fellay, Jacques, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, H.C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, Fellay, Jacques, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.

Subjects
Adult, Male, Genotype, Anti-HIV Agents, CD14, Lipopolysaccharide Receptors, 610 Medicine & health, HIV Infections, Chromosomal translocation, Genome-wide association study, Biology, Fatty Acid-Binding Proteins, Virus Replication, Translocation, Genetic, 10234 Clinic for Infectious Diseases, Cohort Studies, Pathogenesis, Major Articles and Brief Reports, Immune system, Genetic variation, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/therapeutic use, Antigens, CD14/blood, Antigens, CD14/metabolism, Biological Markers/blood, Fatty Acid-Binding Proteins/blood, Fatty Acid-Binding Proteins/metabolism, Female, Gene Expression Regulation/physiology, HIV Infections/epidemiology, HIV Infections/genetics, HIV-1/physiology, Switzerland/epidemiology, Viral Load, Virus Replication/physiology, 2725 Infectious Diseases, Virology, 3. Good health, Infectious Diseases, Gene Expression Regulation, Viral replication, Immunology, 10033 Clinic for Immunology, 2723 Immunology and Allergy, HIV-1, Erratum, Viral load, Biomarkers, Switzerland
Abstract

Systemic immune activation, a major determinant of human immunodeficiency virus (HIV) disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. Although human genetic variants influencing HIV load have been identified, it is unknown how much the host genetic background contributes to interindividual differences in other determinants of HIV pathogenesis such as gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty acid–binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble CD14 (sCD14), a marker of lipopolysaccharide bioactivity and microbial translocation. We also assessed the correlations between HIV load, sCD14, and I-FABP. Although we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infection.

Published
2015

6. 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, D. L., Hampel, B., Martin, E., Kouyos, R., Kusejko, K., Grube, C., Flepp, M., Stöckle, M., Conen, A., Béguelin, C., Schmid, P., Delaloye, J., Rougemont, M., Bernasconi, E., Rauch, A., Günthard, H. F., Böni, J., Fehr, J. S., Anagnostopoulos, A., Battegay, M., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fellay, J., Furrer, H., Fux, C. A., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Tejada, B. M., Marzolini, C., Metzner, K. J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rudin, C., Scherrer, A. U., Speck, R., Philip TARR, Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.

7. HIV Transmission Chains Exhibit Greater HLA-B Homogeneity Than Randomly Expected

Author

Huyen Nguyen, Thorball, Christian W., Fellay, Jacques, Boni, Jurg, Yerly, Sabine, Perreau, Matthieu, Klimkait, Thomas, Kusejko, Katharina, Bachmann, Nadine, Chaudron, Sandra E., Paioni, Paolo, Thurnheer, Maria C., Battegay, Manuel, Cavassini, Matthias, Vernazza, Pietro, Bernasconi, Enos, Gunthard, Huldrych F., Kouyos, Roger, Anagnostopoulos, A., Braun, D. L., Bucher, H. C., Calmy, A., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Furrer, H., Fux, C. A., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kahlert, C., Kaiser, L., Keiser, O., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., de Tejada, B. Martinez, Marzolini, C., Metzner, K. J., Mueller, N., Nicca, D., Pantaleo, G., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Trkola, A., Wandeler, G., and Weber, R.

Subjects
concordance, immune control, transmission chains, association, virus diseases, determinants, restriction, t-cell responses, escape mutations, hla, coevolution, evolution, class-i, mate choice
Abstract

Background: HIV's capacity to escape immune recognition by human leukocyte antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to the host HLA type and could better improve therapeutic strategies against HIV., Materials and Methods: Three hundred one to 325 transmission pairs and 469-496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA class I data were compiled at 3 specificity levels: 4-digit, 2-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as 2 measures: the proportion of transmission pairs, which are HLA concordant, and the average percentage of allele matches within all clusters. These measures were compared with the mean value across randomizations with randomly assorted individuals., Results: We repeated the analysis for different HLA classification levels and separately for HLA-A,-B, and-C. Subanalyses by the risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs. 0.251, P value = 0.009; supertype clusters: 0.659 vs. 0.611, P value = 0.002; supertype pairs: 0.655 vs. 0.608, P value = 0.014). Risk group restriction caused the effect to disappear for men-who-have-sexwith- men but not for other risk groups. We also examined if protective HLA alleles B27 and B57 were under-or overrepresented in the transmission chains, although this yielded no significant pattern., Conclusions: The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.

8. Impact of Genetic and Nongenetic Factors on Body Mass Index and Waist-Hip Ratio Change in HIV-Infected Individuals Initiating Antiretroviral Therapy

Author

Enos Bernasconi, Hansjakob Furrer, Sebastian Haubitz, Chantal Csajka, Christian Hammer, Monia Guidi, Barbara Hasse, Philip E. Tarr, Aziz Chaouch, Matthias Cavassini, Alexandra Calmy, Jacques Fellay, Thierry Buclin, Christian W. Thorball, Catalina Barceló, Alexandra U. Scherrer, Swiss HIV Cohort Study, Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., Yerly, S., Anagnostopoulos, A, Battegay, M, Böni, J, Braun, D L, Bucher, H C, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fux, C A, Günthard, H F, Haerry, D, Hirsch, H H, Hoffmann, M, Hösli, I, Huber, M, Kahlert, C R, Kaiser, L, Keiser, Olivia, Klimkait, T, Kouyos, R D, Kovari, H, Ledergerber, B, Martinetti, G, Martinez De Tejada Weber, Begona, Marzolini, C, Metzner, K J, Müller, N, Nicca, D, Paioni, P, Pantaleo, G, Perreau, M, Rauch, A, Rudin, C, Schmid, P, Speck, R, Stöckle, M, Trkola, A, Vernazza, P, Weber, R, and Yerly Ferrillo, Sabine

Subjects
0301 basic medicine, obesity, cardiovascular-disease, Overweight, 0302 clinical medicine, Waist–hip ratio, genetics, 030212 general & internal medicine, skin and connective tissue diseases, Body mass index, Abdominal obesity, risk, ddc:616, 2. Zero hunger, ddc:615, food and beverages, Antiretroviral therapy, 3. Good health, Infectious Diseases, Oncology, randomized controlled-trial, medicine.symptom, Nadir CD4 cell count, Cohort study, medicine.medical_specialty, Waist, weight-gain, antiretroviral therapy, united-states, 030106 microbiology, 610 Medicine & health, body mass index, metabolic syndrome, abdominal obesity, human-immunodeficiency-virus, fat changes, 03 medical and health sciences, Internal medicine, Genetics, Major Article, medicine, Obesity, business.industry, Weight change, association, nutritional and metabolic diseases, nadir cd4 cell count, Odds ratio, Waist-hip ratio, nadir CD4 cell count, waist-hip ratio, sense organs, business
Abstract

Objective. There is limited data on abdominal obesity and the influence of genetics on weight change after ant iretroviral therapy (ART) initiation. We assessed body mass index (BMI) and waist hip ration (WHR) change over time in the Swiss HIV Cohort study (SHCS)., Methods. Mixed-effects models characterizing BMI and WHR change over time in 1090 SHCS participants initiating ART between 2005 and 2015 were developed and used to quantify the influence of demographics, clinical factors, and genetic background., Results. Individuals with CD4 nadir = 200, and 2.8 times more WHR than individuals with >= 100 (P < .001) during the first 1.5 and 2.5 years after ART initiation, respectively. The risk of being overweight or obese after 1.5 years increased with CD4 nadir = 200 (OR, 1.69; 95% CI, 1.26-2.32), persisting after 10 years of ART. The risk of abdominal obesity after 2.5 years increased with CD4 nadir = 100 (OR, 1.35; 95% CI, 1.17-1.54 [in men]; OR, 1.36; 95% CI, 1.18-1.57 [in women]), persisting after 10 years of ART No significant differences were found across antiretroviral drug classes or genetic scores., Conclusions. The risk of general and abdominal obesity increased with CD4 nadir

Published
2020

9. The influence of human genetic variation on Epstein-Barr virus sequence diversity

Author

Jacques Fellay, Huldrych F. Günthard, Sina Rüeger, Nina Khanna, Evgeny M. Zdobnov, Olivier Naret, Judith Breuer, Andri Rauch, Christian R Kahlert, Daniel P. Depledge, Dylan Lawless, Paul J. McLaren, Sofia Morfopoulou, Enos Bernasconi, Christian Hammer, Matthias Cavassini, Alexis Loetscher, Swiss HIV Cohort Study, Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D., Bucher, H., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., de Tejada, B.M., Marzolini, C., Metzner, K., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., and Yerly, S.

Subjects
Epstein-Barr Virus Infections, Herpesvirus 4, Human, Science, 610 Medicine & health, Human genetic variation, Genome, Viral, Biology, medicine.disease_cause, Genome-wide association studies, Genome, Article, Virus, Cohort Studies, Immune system, hemic and lymphatic diseases, Immunogenetics, medicine, Humans, Author Correction, Pathogen, Gene, Genetics, Multidisciplinary, Genetic Variation, High-Throughput Nucleotide Sequencing, Epstein–Barr virus, Viral infection, Epstein-Barr Virus Infections/virology, Herpesvirus 4, Human/genetics, Medicine, Human genome
Abstract

Epstein–Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4 + T cell count 3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.

Published
2020

10. High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with hepatitis C virus

Author

Nicolas Müller, M. Huber, Barbara Hasse, Matthias Hoffmann, Christoph Rudin, Thierry Calandra, Gladys Martinetti, Thomas Klimkait, A. Anagnostopoulos, Helen Kovari, Catia Marzolini, Enos Bernasconi, B Martinez de Tejada, Laurent Kaiser, Karin J. Metzner, Tytti Heinonen, Dominique L Braun, M. Cavassini, Giuseppe Pantaleo, P. Vernazza, Philip E. Tarr, Jürg Böni, Irene T. Schrijver, Marcel Stöckle, Jacques Fellay, Manuel Battegay, Khalid Ohmiti, K. Aebi-Popp, D Haerry, Rainer Weber, Alexandra U. Scherrer, G. Dollenmaier, Hansjakob Furrer, Thierry Roger, Jacobus Herderschee, Christian R Kahlert, Angela Ciuffi, Günthard Hf, Craig Fenwick, Hans H. Hirsch, A. Calmy, Andri Rauch, Irene Hösli, M. Perreau, A. Trkola, Patrick Schmid, Christoph A Fux, G. Pantaleo, Matthias Cavassini, Paolo Paioni, Sabine Yerly, Roger D. Kouyos, Jan Fehr, Olivia Keiser, Dunja Nicca, M Egger, L Elzi, Darius Moradpour, Gilles Wandeler, B Ledergerber, Roberto F. Speck, Heiner C. Bucher, Swiss HIV Cohort Study, Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.

Subjects
Microbiology (medical), business.industry, Hepatitis C virus, HIV Infections, Hepacivirus, General Medicine, CD8-Positive T-Lymphocytes, Hepatitis C, Chronic, medicine.disease_cause, Acquired immune system, Antiviral Agents, Hepatitis C, Virus, Blood cell, Infectious Diseases, medicine.anatomical_structure, Immune system, Interquartile range, Immunity, Immunology, Humans, Cytotoxic T cell, Medicine, Antiviral Agents/therapeutic use, HIV Infections/complications, HIV Infections/drug therapy, Hepatitis C/complications, Hepatitis C/drug therapy, Hepatitis C, Chronic/drug therapy, Adaptive immunity, Direct-acting antiviral therapy, Human immunodeficiency virus, Innate immunity, Mass cytometry, Single cell, business
Abstract

Objectives Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV before and after DAA therapy. Methods Before and 12 weeks after sustained virological response (SVR12) to DAA therapy, 22 cell populations were analysed by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with (ten patients) or without (ten patients) human immunodeficiency virus (HIV) infection. Results HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median, interquartile range (IQR); control, HCV, HCV/HIV) of intermediate monocytes (1.2, IQR 0.47–1.46; 1.76, IQR 0.83–2.66; 0.78, IQR 0.28–1.77), non-classical monocytes (1.11, IQR 0.49–1.26; 0.9, IQR 0.18–0.99; 0.54, IQR 0.28–1.77), conventional dendritic cells type 2 (0.55, IQR 0.35–0.59; 0.31, IQR 0.16–0.38; 0.19, IQR 0.11–0.36) and CD56dim natural killer cells (8.08, IQR 5.34–9.79; 4.72, IQR 2.59–6.05) 3.61, IQR 2.98–5.07) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07, IQR 0.06–0.10; 0.10, IQR 0.09–0.19; 0.19, IQR 0.12–0.25), activated CD4 T cells (0.28, IQR 0.21–0.36; 0.56, IQR 0.33–0.77; 0.40, IQR 0.22–0.53) and activated CD8 T cells (0.23, IQR 0.14–0.42; 0.74, IQR 0.30–1.65; 0.80, IQR 0.58–1.16) were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV- and HCV/HIV-infected patients, respectively. Most alterations persisted at SVR12. Conclusions Chronic HCV and HCV/HIV infections induce profound and durable perturbations of innate and adaptive immune homeostasis.

Published
2022

11. Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis

Author

Hovaguimian, Frédérique, Günthard, Huldrych F, Hauser, Christoph, Conen, Anna, Bernasconi, Enos, Calmy, Alexandra, Cavassini, Matthias, Seneghini, Marco, Marzel, Alex, Heinrich, Henriette, Scherrer, Alexandra, Riou, Julien, Spoerri, Adrian, Schmidlin, Kurt, Balakrishna, Suraj, Braun, Dominique L, Rampini, Silvana K, Fehr, Jan S, Kouyos, Roger D, Swiss HIV Cohort Study, University of Zurich, Hovaguimian, Frédérique, Swiss HIV Cohort Study, Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.

Subjects
0301 basic medicine, 10028 Institute of Medical Virology, Data Analysis, Male, Pediatrics, Epidemiology, medicine.medical_treatment, Human immunodeficiency virus (HIV), General Physics and Astronomy, HIV Infections, medicine.disease_cause, Men who have sex with men, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, 610 Medicine & health, First episode, Multidisciplinary, Probabilistic data networks, virus diseases, 3100 General Physics and Astronomy, cardiovascular system, Female, Post-Exposure Prophylaxis, 360 Social problems & social services, Cohort study, circulatory and respiratory physiology, Adult, medicine.medical_specialty, Science, education, MEDLINE, 1600 General Chemistry, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, medicine, Humans, Post-exposure prophylaxis, Preventive medicine, business.industry, General Chemistry, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 030112 virology, HIV Infections/diagnosis, HIV Infections/prevention & control, Long term risk, Observational study, 10029 Clinic and Policlinic for Internal Medicine, business
Abstract

Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis., Individuals seeking post-exposure prophylaxis (PEP) for HIV may represent an important risk group for future HIV infection. Here the authors find HIV infections at long-term follow-up in 22 of 348 men who have sex with men, and 0 of 623 other PEP seekers.

Published
2020

12. Trends in HCV treatment uptake, efficacy and impact on liver fibrosis in the Swiss HIV Cohort Study

Author

Béguelin, Charles, Suter, Annatina, Bernasconi, Enos, Fehr, Jan, Kovari, Helen, Bucher, Heiner C, Stoeckle, Marcel, Cavassini, Mathias, Rougemont, Mathieu, Schmid, Patrick, Wandeler, Gilles, Rauch, Andri, Swiss HIV Cohort Study, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Böni, J., Braun, D.L., Calmy, A., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Ledergerber, B., Martinetti, G., Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Pantaleo, G., Paioni, P., Rudin, C., Scherrer, A.U., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Béguelin, Charles

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Sustained Virologic Response, Hepatitis C virus, Liver fibrosis, Human immunodeficiency virus (HIV), 610 Medicine & health, HIV Infections, Hepacivirus, medicine.disease_cause, Antiviral Agents, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, ddc:616, Hepatology, Coinfection, business.industry, Incidence (epidemiology), virus diseases, HIV, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Hepatitis C, Chronic, Middle Aged, medicine.disease, Institutional repository, 10036 Medical Clinic, Antiviral Agents/therapeutic use, Coinfection/drug therapy, Drug Therapy, Combination, Female, HIV/genetics, HIV Infections/complications, HIV Infections/drug therapy, Hepatitis C, Chronic/complications, Hepatitis C, Chronic/drug therapy, Liver Cirrhosis/epidemiology, Liver Cirrhosis/virology, Switzerland/epidemiology, DAA, HCV treatment, fibrosis, long-term trends, uptake and efficacy, Immunology, 2721 Hepatology, 030211 gastroenterology & hepatology, business, Switzerland, Cohort study
Abstract

BACKGROUND & AIMS Hepatitis C virus (HCV) therapies with interferon-free second-generation direct-acting antiviral agents (DAAs) are highly effective and well tolerated. They have the potential to increase treatment eligibility and efficacy in HIV-infected patients. We assessed the impact of DAAs on treatment uptake, efficacy as well as its impact on the burden of liver disease in the Swiss HIV Cohort Study (SHCS). METHODS We describe clinical and virological characteristics of patients treated with second generation DAAs. We compared treatment incidence, sustained virological response (SVR)12 and liver fibrosis stages between three time periods: period 1, 01/2009-08/2011 (prior to the availability of DAAs); period 2, 09/2011-03/2014 (first generation DAAs); period 3, 04/2014-12/2015 (second generation DAAs). RESULTS At the beginning of the third period, 876 SHCS participants had a chronic HCV infection of whom 180 (20%) started treatment with a second generation DAA. Three- quarters of them had advanced liver fibrosis (Metavir≥3) of whom 80% were cirrhotics. SVR12 was achieved in 173/180 (96%) patients, 3 patients died and 4 experienced a virological failure. Over the three time periods, treatment uptake (4.5/100py, 5.7/100py, 22.4/100py) and efficacy (54%, 70%, 96% SVR12) continuously increased. The number of cirrhotic patients with replicating HCV infection in the SHCS declined from 25% at the beginning to 12% at the end of the last period. CONCLUSIONS After the introduction of second generation DAAs we observed an increase in treatment uptake and efficacy which resulted in a significant reduction in the number of cirrhotic patients with replicating HCV infection in the SHCS. This article is protected by copyright. All rights reserved.

Published
2017

13. Polypharmacy, Drug-Drug Interactions, and Inappropriate Drugs: New Challenges in the Aging Population With HIV

Author

Catia Marzolini, Thierry Buclin, Françoise Livio, Manuel Battegay, Monia Guidi, Laurent A. Decosterd, Chantal Csajka, Susana Alves Saldanha, Marcel Stoeckle, Perrine Courlet, Matthias Cavassini, 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, Drug, medicine.medical_specialty, Population ageing, Chronic condition, HIV, aging, drug–drug interactions, elderly, inappropriate drugs, polypharmacy, media_common.quotation_subject, 030106 microbiology, Beers Criteria, Human immunodeficiency virus (HIV), medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Major Article, 030212 general & internal medicine, media_common, Polypharmacy, Geriatrics, business.industry, Infectious Diseases, Oncology, business, Cohort study
Abstract

Background Antiretroviral therapy has transformed HIV infection from a deadly into a chronic condition. Aging people with HIV (PWH) are at higher risk of polypharmacy, potential drug–drug interactions (DDIs), and potentially inappropriate medications (PIMs). This study aims to compare prescribed drugs, polypharmacy, and potential DDIs between young ( Methods PWH from 2 centers within the Swiss HIV Cohort Study were asked to fill in a form with all their current medications. Polypharmacy was defined as being on ≥5 non-HIV drugs. PIMs were evaluated using Beers criteria. Potential DDIs for the most prescribed therapeutic classes were screened with the Liverpool interaction database. Results Among the 996 PWH included, 122 were ≥65 years old. Polypharmacy was more frequent in the elderly group (44% vs 12%). Medications and potential DDIs differed according to the age group: cardiovascular drugs and related potential DDIs were more common in the elderly group (73% of forms included ≥1 cardiovascular drug; 11% of cardiovascular drugs involved potential DDIs), whereas central nervous system drugs were more prescribed and involved in potential DDIs in younger PWH (26%, 11%). Potential DDIs were mostly managed through dosage adjustments. PIMs were found in 31% of the elderly group. Conclusions Potential DDIs remain common, and PIMs constitute an additional burden for the elderly. It is important that prescribers develop and maintain a proactive approach for the recognition and management of DDIs and other prescribing issues frequently encountered in geriatric medicine.

Published
2019

14. Impact of Direct-Acting Antivirals on the Burden of HCV Infection Among Persons Who Inject Drugs and Men Who Have Sex With Men in the Swiss HIV Cohort Study

Author

Marcel Stoeckle, Gilles Wandeler, Luisa Salazar-Vizcaya, Jan Fehr, Matthias Hoffmann, Enos Bernasconi, Mathieu Rougemont, Matthias Cavassini, Andri Rauch, Charles Béguelin, Dominique L Braun, University of Zurich, Béguelin, Charles, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Pantaleo, G., Paioni, P., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., and Yerly, S.

Subjects
medicine.medical_specialty, Hepatitis C virus, Human immunodeficiency virus (HIV), 610 Medicine & health, medicine.disease_cause, DIRECT ACTING ANTIVIRALS, Men who have sex with men, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, 360 Social problems & social services, Internal medicine, medicine, MSM, 030212 general & internal medicine, PWID, DAA, business.industry, Brief Report, virus diseases, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Hepatitis C, medicine.disease, 3. Good health, 2728 Neurology (clinical), Infectious Diseases, Oncology, Viral replication, HCV, viral replication, 2730 Oncology, 030211 gastroenterology & hepatology, business, Cohort study
Abstract

In the Swiss HIV Cohort Study, the number of people who inject drugs with replicating hepatitis C virus (HCV) infection decreased substantially after the introduction of direct-acting antivirals (DAAs). Among men who have sex with men, the increase in DAA uptake and efficacy was counterbalanced by frequent incident HCV infections.

Published
2018

15. Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study

Author

Yang Wan-Lin, Kouyos Roger D., Scherrer Alexandra U., Boeni Juerg, Shah Cyril, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Hirzel Cedric, Battegay Manuel, Cavassini Matthias, Bernasconi Enos, Vernazza Pietro, Held Leonhard, Ledergerber Bruno, Guenthard Huldrych F., Study Swiss HIV Cohort, University of Zurich, Swiss HIV Cohort Study (SHCS), Swiss HIV Cohort Study SHCS, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.

Subjects
Male, 10028 Institute of Medical Virology, Adult, Antiretroviral Therapy, Highly Active/methods, Drug Resistance, Viral, Female, HIV Infections/drug therapy, HIV-1, Humans, Middle Aged, Nucleosides/therapeutic use, Nucleotides/therapeutic use, Reverse Transcriptase Inhibitors/therapeutic use, Switzerland, Treatment Failure, Drug Resistance, HIV Infections, 01 natural sciences, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, Abacavir, Antiretroviral Therapy, Highly Active, 2736 Pharmacology (medical), Medicine, Pharmacology (medical), Viral, 030212 general & internal medicine, ddc:616, education.field_of_study, Nucleotides, virus diseases, Lamivudine, Nucleosides, 3. Good health, 3004 Pharmacology, Infectious Diseases, Reverse Transcriptase Inhibitors, medicine.drug, Microbiology (medical), medicine.medical_specialty, Highly Active/methods, Efavirenz, Nevirapine, Population, Antiretroviral Therapy, 610 Medicine & health, Emtricitabine, 03 medical and health sciences, Zidovudine, Internal medicine, 0101 mathematics, education, Pharmacology, business.industry, 010102 general mathematics, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 2725 Infectious Diseases, Lamivudine/Zidovudine, Virology, chemistry, 10033 Clinic for Immunology, business
Abstract

BACKGROUND The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare. METHODS We included patients starting first-line combination ART (cART) with or switching from first-line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency. RESULTS Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02). CONCLUSIONS Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden.

Published
2015
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16. Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The Swiss HIV Cohort Study

Author

Cornelia, Bayard, Bruno, Ledergerber, Markus, Flepp, Thanh, Lecompte, Estelle, Moulin, Matthias, Hoffmann, Rainer, Weber, Cornelia, Staehelin, Caroline, Di Benedetto, Christoph A, Fux, Philip E, Tarr, Barbara, Hasse, S, Yerly, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nicca, D., Pantaleo, G., Paioni, P., Rauch, A., Rudin, C., Scherrer, A.U., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Weber, R., Yerly, S., University of Zurich, and Hasse, Barbara

Subjects
0301 basic medicine, medicine.medical_specialty, 030106 microbiology, Population, antiretroviral therapy, 610 Medicine & health, avascular bone necrosis, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Major Article, Medicine, 030212 general & internal medicine, Risk factor, education, ddc:616, education.field_of_study, business.industry, Incidence (epidemiology), Case-control study, HIV, Odds ratio, Confidence interval, tenofovir, 3. Good health, Surgery, 2728 Neurology (clinical), Infectious Diseases, Oncology, 2730 Oncology, business, Viral load, Cohort study
Abstract

BackgroundHIV-infected individuals have an increased risk of avascular bone necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors (PI) have been implicated as a risk factor. We aimed to study the associations of ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS).MethodsWe used incidence density sampling to perform a case control study within the Swiss HIV Cohort Study (SHCS) comparing prospectively collected AVN cases and controls by conditional logistic regression analysis. To evaluate the effect of ART, multivariable models were adjusted for HIV transmission risk group, age, alcohol consumption, use of corticosteroids, CD4 nadir, maximum viral load, and pancreatitis.ResultsWe compared 74 AVN cases and 145 controls. Associations with AVN were shown for heterosexual HIV acquisition (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1–10), alcohol consumption (OR, 2.7; 95% CI, 1.3–5.7), and hyperlipidemia (OR, 3.6; 95% CI, 1.4–9.6). After adding ART substances to the multivariable base model, there was evidence of an association for treatment with tenofovir (TDF) >1 year (OR, 4.4; 95% CI, 1.4–14) with AVN. Neither exposure to specific frequently prescribed ART combinations or ART drug classes nor cumulative ART exposure showed any associations with AVN.ConclusionsIn the HIV-infected population, a combination of risk factors such as heterosexual HIV acquisition, moderate to severe alcohol intake, and hyperlipidemia seem to contribute to AVN. ART does not seem to be a relevant risk factor for AVN. The association of prolonged TDF exposure with AVN needs to be confirmed.

Published
2017

17. Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland

Author

Shilaih Mohaned, Marzel Alex, Yang Wan Lin, Scherrer Alexandra U., Schupbach Jorg, Boni Jurg, Yerly Sabine, Hirsch Hans H., Aubert Vincent, Cavassini Matthias, Klimkait Thomas, Vernazza Pietro L., Bernasconi Enos, Furrer Hansjakob, Gunthard Huldrych F., Kouyos Roger, Study Swiss HIV Cohort, Swiss HIV Cohort Study, Battegay, M., Braun, D., Bucher, H., Burton-Jeangros, C., Calmy, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Fux, C., Gorgievski, M., Haerry, D., Hasse, B., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Ledergerber, B., Martinetti, G., de Tejada, B.M., Marzolini, C., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rudin, C., Schöni-Affolter, F., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Weber, R., University of Zurich, and Shilaih, Mohaned

Subjects
Adult, Male, 10028 Institute of Medical Virology, 0301 basic medicine, Multivariate analysis, Genotype, Anti-HIV Agents, Anti-HIV Agents/therapeutic use, Cohort Studies, Drug Resistance, Viral/genetics, Female, HIV Infections/drug therapy, HIV Infections/epidemiology, HIV Infections/transmission, HIV Infections/virology, HIV-1/classification, HIV-1/genetics, HIV-1/isolation & purification, Heterosexuality, Homosexuality, Male, Humans, Middle Aged, Molecular Typing, Multivariate Analysis, Phylogeny, Substance Abuse, Intravenous/drug therapy, Substance Abuse, Intravenous/epidemiology, Substance Abuse, Intravenous/virology, Switzerland/epidemiology, HIV Infections, 610 Medicine & health, Biology, Logistic regression, Article, law.invention, 10234 Clinic for Infectious Diseases, 03 medical and health sciences, 0302 clinical medicine, law, Drug Resistance, Viral, 030212 general & internal medicine, Substance Abuse, Intravenous, ddc:616, Genetics, 1000 Multidisciplinary, Multidisciplinary, Phylogenetic tree, Outbreak, Confidence interval, 3. Good health, 030104 developmental biology, Transmission (mechanics), HIV-1, Switzerland, Demography, Cohort study
Abstract

Targeting hard-to-reach/marginalized populations is essential for preventing HIV-transmission. A unique opportunity to identify such populations in Switzerland is provided by a database of all genotypic-resistance-tests from Switzerland, including both sequences from the Swiss HIV Cohort Study (SHCS) and non-cohort sequences. A phylogenetic tree was built using 11,127 SHCS and 2,875 Swiss non-SHCS sequences. Demographics were imputed for non-SHCS patients using a phylogenetic proximity approach. Factors associated with non-cohort outbreaks were determined using logistic regression. Non-B subtype (univariable odds-ratio (OR): 1.9; 95% confidence interval (CI): 1.8–2.1), female gender (OR: 1.6; 95% CI: 1.4–1.7), black ethnicity (OR: 1.9; 95% CI: 1.7–2.1) and heterosexual transmission group (OR:1.8; 95% CI: 1.6–2.0), were all associated with underrepresentation in the SHCS. We found 344 purely non-SHCS transmission clusters, however, these outbreaks were small (median 2, maximum 7 patients) with a strong overlap with the SHCS’. 65% of non-SHCS sequences were part of clusters composed of >= 50% SHCS sequences. Our data suggests that marginalized-populations are underrepresented in the SHCS. However, the limited size of outbreaks among non-SHCS patients in-care implies that no major HIV outbreak in Switzerland was missed by the SHCS surveillance. This study demonstrates the potential of sequence data to assess and extend the scope of infectious-disease surveillance.

Published
2016

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

Author

Hans H. Hirsch, A. Calmy, Irene Hösli, Nicolas Müller, Manuel Battegay, Pietro Vernazza, Laurent Kaiser, G. Dollenmaier, Andri Rauch, Cyril Shah, Franziska Schöni-Affolter, Sabine Yerly, S Yerly, Olivia Keiser, Karin J. Metzner, Jörg Schüpbach, Patrick Schmid, Barbara Hasse, E Bernasconi, Roger D. Kouyos, Christian R Kahlert, Günthard Hf, Jan Fehr, Meri Gorgievski, P. Vernazza, Matthias Hoffmann, Stephan Regenass, M. Cavassini, B Martinez de Tejada, Gladys Martinetti, Jürg Böni, Hansjakob Furrer, RD Kouyos, C. A. Fux, B. Ledergerber, Leonhard Held, Christoph Rudin, Dunja Nicca, Martin Rickenbach, M Egger, Rainer Weber, Alexandra U. Scherrer, Huldrych F. Günthard, H Furrer, G. Pantaleo, Jacques Fellay, A. Telenti, D Haerry, Roberto F. Speck, Heiner C. Bucher, David Nadal, Matthias Cavassini, Vincent Aubert, Helen Kovari, Thomas Klimkait, Bruno Ledergerber, Enos Bernasconi, T Klimkait, V Aubert, L. Elzi, Philip E. Tarr, M Battegay, Alexandra Trkola, Wan-Lin Yang, Claudine Burton-Jeangros, J Böni, Swiss HIV Cohort Study, Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schöni-Affolter, F., Schmid, P., Schüpbach, J., Speck, R., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Günthard, Huldrych F

Subjects
10028 Institute of Medical Virology, Male, HIV Infections, Drug resistance, Rate ratio, 10234 Clinic for Infectious Diseases, Cohort Studies, Editorial Commentaries, 0302 clinical medicine, Prevalence, Immunology and Allergy, 030212 general & internal medicine, Prospective Studies, ddc:616, 0303 health sciences, education.field_of_study, Resistance mutation, 3. Good health, Infectious Diseases, HIV, transmission, drug resistance, recently infected, fitness, symbols, 2723 Immunology and Allergy, Female, Viral load, Cohort study, Adult, medicine.medical_specialty, Genotype, Anti-HIV Agents, Population, Mutation, Missense, 610 Medicine & health, 03 medical and health sciences, symbols.namesake, Internal medicine, Drug Resistance, Viral, medicine, Humans, Poisson regression, education, antiretroviral drugs, 030306 microbiology, business.industry, acquired resistance, Odds ratio, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), 2725 Infectious Diseases, biochemical phenomena, metabolism, and nutrition, transmitted resistance, Immunology, 10033 Clinic for Immunology, HIV-1, business
Abstract

BACKGROUND: Transmitted human immunodeficiency virus type 1 (HIV) drug resistance (TDR) mutations are transmitted from nonresponding patients (defined as patients with no initial response to treatment and those with an initial response for whom treatment later failed) or from patients who are naive to treatment. Although the prevalence of drug resistance in patients who are not responding to treatment has declined in developed countries, the prevalence of TDR mutations has not. Mechanisms causing this paradox are poorly explored. METHODS: We included recently infected, treatment-naive patients with genotypic resistance tests performed ≤1 year after infection and before 2013. Potential risk factors for TDR mutations were analyzed using logistic regression. The association between the prevalence of TDR mutations and population viral load (PVL) among treated patients during 1997-2011 was estimated with Poisson regression for all TDR mutations and individually for the most frequent resistance mutations against each drug class (ie, M184V/L90M/K103N). RESULTS: We included 2421 recently infected, treatment-naive patients and 5399 patients with no response to treatment. The prevalence of TDR mutations fluctuated considerably over time. Two opposing developments could explain these fluctuations: generally continuous increases in the prevalence of TDR mutations (odds ratio, 1.13; P = .010), punctuated by sharp decreases in the prevalence when new drug classes were introduced. Overall, the prevalence of TDR mutations increased with decreasing PVL (rate ratio [RR], 0.91 per 1000 decrease in PVL; P = .033). Additionally, we observed that the transmitted high-fitness-cost mutation M184V was positively associated with the PVL of nonresponding patients carrying M184V (RR, 1.50 per 100 increase in PVL; P < .001). Such association was absent for K103N (RR, 1.00 per 100 increase in PVL; P = .99) and negative for L90M (RR, 0.75 per 100 increase in PVL; P = .022). CONCLUSIONS: Transmission of antiretroviral drug resistance is temporarily reduced by the introduction of new drug classes and driven by nonresponding and treatment-naive patients. These findings suggest a continuous need for new drugs, early detection/treatment of HIV-1 infection.

Published
2014

19. Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs

Author

Oberle Corinna S, Joos Beda, Rusert Peter, Campbell Nottania K, Beauparlant David, Kuster Herbert, Weber Jacqueline, Schenkel Corinne D, Scherrer Alexandra U, Magnus Carsten, Kouyos Roger, Rieder Philip, Niederöst Barbara, Braun Dominique L, Pavlovic Jovan, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Trkola Alexandra, Metzner Karin J, Günthard Huldrych F, Swiss HIV Cohort Study (SHCS), Aubert, V., Battegay, M., Bernasconi, E., Böni, J., Braun, D., Bucher, H., Burton-Jeangros, C., Calmy, A., Cavassini, M., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K., Müller, N., Nadal, D., Nicca, D., Pantaleo, G., Rauch, A., Regenass, S., Rudin, C., Schöni-Affolter, F., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Günthard, Huldrych F

Subjects
10028 Institute of Medical Virology, 0301 basic medicine, Male, viruses, HIV Infections, Neutralization, law.invention, 10234 Clinic for Infectious Diseases, Env Gene Products, law, Leukocytes, ddc:616, education.field_of_study, Replicative capacity, env Gene Products, Human Immunodeficiency Virus, Reply to Correspondence, Neutralizing/blood/immunology, Homosexuality, Phenotype, 3. Good health, Infectious Diseases, Transmission (mechanics), Acute Disease, Female, Antibody, Mononuclear/drug effects/virology, Sequence Analysis, Population, Entry, 610 Medicine & health, Biology, Antibodies, Neutralizing/blood, Antibodies, Neutralizing/immunology, Genetic Variation, HIV Infections/transmission, HIV Infections/virology, HIV-1/genetics, HIV-1/isolation & purification, HIV-1/physiology, Homosexuality, Male, Humans, Interferon-alpha/pharmacology, Leukocytes, Mononuclear/drug effects, Leukocytes, Mononuclear/virology, Neutralization Tests, Sequence Analysis, DNA, Stochastic Processes, Viral Tropism, Virus Internalization, env Gene Products, Human Immunodeficiency Virus/genetics, env Gene Products, Human Immunodeficiency Virus/immunology, Virus, Antibodies, 03 medical and health sciences, HIV-1, Transmission, Envelope, IFNalpha, Virology, education, Human Immunodeficiency Virus/genetics/immunology, Genetic diversity, HIV-1/genetics/isolation & purification/physiology, Host (biology), Research, Interferon-alpha, 2725 Infectious Diseases, HIV Infections/transmission/virology, DNA, Antibodies, Neutralizing, 030104 developmental biology, 2406 Virology, Leukocytes, Mononuclear, biology.protein, IFNα
Abstract

Background Mucosal HIV-1 transmission predominantly results in a single transmitted/founder (T/F) virus establishing infection in the new host despite the generally high genetic diversity of the transmitter virus population. To what extent HIV-1 transmission is a stochastic process or driven by selective forces that allow T/F viruses best to overcome bottlenecks in transmission has not been conclusively resolved. Building on prior investigations that suggest HIV-1 envelope (Env) features to contribute in the selection process during transmission, we compared phenotypic virus characteristics of nine HIV-1 subtype B transmission pairs, six men who have sex with men and three male-to-female transmission pairs. Results All recipients were identified early in acute infection and harbored based on extensive sequencing analysis a single T/F virus allowing a controlled analysis of virus properties in matched transmission pairs. Recipient and transmitter viruses from the closest time point to transmission showed no signs of selection for specific Env modifications such as variable loop length and glycosylation. Recipient viruses were resistant to circulating plasma antibodies of the transmitter and also showed no altered sensitivity to a large panel of entry inhibitors and neutralizing antibodies. The recipient virus did not consistently differ from the transmitter virus in terms of entry kinetics, cell–cell transmission and replicative capacity in primary cells. Our paired analysis revealed a higher sensitivity of several recipient virus isolates to interferon-α (IFNα) which suggests that resistance to IFNα cannot be a general driving force in T/F establishment. Conclusions With the exception of increased IFNα sensitivity, none of the phenotypic virus properties we investigated clearly distinguished T/F viruses from their matched transmitter viruses supporting the notion that at least in subtype B infection HIV-1 transmission is to a considerable extent stochastic. Electronic supplementary material The online version of this article (doi:10.1186/s12977-016-0299-0) contains supplementary material, which is available to authorized users.

Published
2016

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