PMID- 31107301 OWN - NLM STAT- MEDLINE DCOM- 20200413 LR - 20200930 IS - 1944-7884 (Electronic) IS - 1525-4135 (Linking) VI - 81 IP - 5 DP - 2019 Aug 15 TI - HIV Transmission Chains Exhibit Greater HLA-B Homogeneity Than Randomly Expected. PG - 508-515 LID - 10.1097/QAI.0000000000002077 [doi] AB - 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-sex-with-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. FAU - Nguyen, Huyen AU - Nguyen H AD - Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. AD - Institute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. FAU - Thorball, Christian W AU - Thorball CW AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland. AD - Swiss Institute of Bioinformatics, Lausanne, Switzerland. FAU - Fellay, Jacques AU - Fellay J AD - School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland. AD - Swiss Institute of Bioinformatics, Lausanne, Switzerland. FAU - Boni, Jurg AU - Boni J AD - Institute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. FAU - Yerly, Sabine AU - Yerly S AD - Laboratory of Virology, Geneva University Hospital, University of Geneva, Geneva, Switzerland. FAU - Perreau, Matthieu AU - Perreau M AD - Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland. FAU - Klimkait, Thomas AU - Klimkait T AD - Department of Biomedicine, University of Basel, Basel, Switzerland. FAU - Kusejko, Katharina AU - Kusejko K AD - Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. AD - Institute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. FAU - Bachmann, Nadine AU - Bachmann N AD - Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. AD - Institute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. FAU - Chaudron, Sandra E AU - Chaudron SE AD - Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. AD - Institute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. FAU - Paioni, Paolo AU - Paioni P AD - Division of Infectious Diseases and Hospital Epidemiology, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. FAU - Thurnheer, Maria C AU - Thurnheer MC AD - University Clinic of Infectious Diseases, University Hospital of Bern, University of Bern, Bern, Switzerland. FAU - Battegay, Manuel AU - Battegay M AD - Infectious Diseases and Infection Control Clinic, Department of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland. FAU - Cavassini, Matthias AU - Cavassini M AD - Department of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. FAU - Vernazza, Pietro AU - Vernazza P AD - Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland. FAU - Bernasconi, Enos AU - Bernasconi E AD - Division of Infectious Diseases, Regional Hospital, Lugano, Switzerland. FAU - Gunthard, Huldrych F AU - Gunthard HF AD - Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. AD - Institute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. FAU - Kouyos, Roger AU - Kouyos R AD - Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. AD - Institute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland. CN - Swiss HIV Cohort Study LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Acquir Immune Defic Syndr JT - Journal of acquired immune deficiency syndromes (1999) JID - 100892005 RN - 0 (HLA-A Antigens) RN - 0 (HLA-B Antigens) RN - 0 (HLA-C Antigens) SB - IM MH - *Genetic Predisposition to Disease MH - HIV Infections/*genetics/*transmission MH - HLA-A Antigens/*genetics MH - HLA-B Antigens/*genetics MH - HLA-C Antigens/*genetics MH - Humans MH - Switzerland/epidemiology EDAT- 2019/05/21 06:00 MHDA- 2020/04/14 06:00 CRDT- 2019/05/21 06:00 PHST- 2019/05/21 06:00 [pubmed] PHST- 2020/04/14 06:00 [medline] PHST- 2019/05/21 06:00 [entrez] AID - 10.1097/QAI.0000000000002077 [doi] PST - ppublish SO - J Acquir Immune Defic Syndr. 2019 Aug 15;81(5):508-515. doi: 10.1097/QAI.0000000000002077.