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

Nguyen, Huyen MSca,b; Thorball, Christian W. MScc,d; Fellay, Jacques MDc,d; Böni, Jürg PhDb; Yerly, Sabine PhDe; Perreau, Matthieu PhDf; Klimkait, Thomas PhDg; Kusejko, Katharina PhDa,b; Bachmann, Nadine MSca,b; Chaudron, Sandra E. MSca,b; Paioni, Paolo MDh; Thurnheer, Maria C. MDi; Battegay, Manuel MDj; Cavassini, Matthias MDk; Vernazza, Pietro MDl; Bernasconi, Enos MDm; Günthard, Huldrych F. MDa,b; Kouyos, Roger PhDa,b the Swiss HIV Cohort Study

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15, 2019 - Volume 81 - Issue 5 - p 508–515
doi: 10.1097/QAI.0000000000002077
Epidemiology
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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.

aDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland;

bInstitute of Medical Virology, Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland;

cSchool of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland;

dSwiss Institute of Bioinformatics, Lausanne, Switzerland;

eLaboratory of Virology, Geneva University Hospital, University of Geneva, Geneva, Switzerland;

fDivision of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland;

gDepartment of Biomedicine, University of Basel, Basel, Switzerland;

hDivision of Infectious Diseases and Hospital Epidemiology, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland;

iUniversity Clinic of Infectious Diseases, University Hospital of Bern, University of Bern, Bern, Switzerland;

jInfectious Diseases and Infection Control Clinic, Department of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland;

kDepartment of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland;

lDivision of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; and

mDivision of Infectious Diseases, Regional Hospital, Lugano, Switzerland.

Correspondence to: Huyen Nguyen, MSc, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, Rämistrasse 100, Zürich CH-8091 (e-mail: Huyen.nguyen@usz.ch).

Supported by the Swiss National Science Foundation (Grant numbers BSSGI0_155851, 33CS30_177499 to H.F.G.). H.F.G. was supported by the Swiss National Science Foundation (Grant number 179571). Furthermore, this study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (Grant number 148522), by the SHCS Research Foundation, by the Yvonne Jacob Foundation (to H.F.G.), by the clinical research priority program of the University of Zurich Viral infectious diseases, ZPHI (to H.F.G.), and the University of Zurich University Research Priority Program: Evolution in Action: From Genomes to Ecosystems (Grant number U-702-26-01, to R.K.). H.F.G. has received an unrestricted research Grant from Gilead to the SHCS Research Foundation.

Presented at Conference on Retroviruses and Opportunistic Infections (CROI); March 4–7, 2018; Boston, MA.

H.F.G. has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Sandoz and Mepha; and travel reimbursement from Gilead. M.B. has received research or educational grants by AbbVie AG, Gilead Sciences Switzerland Sàrl, Janssen-Cilag AG, MSD Merck Sharp & Dohme AG, and ViiV Healthcare GmbH. E.B. has received fees for his institution for participation to advisory board from MSD, Gilead Sciences, ViiV Healthcare, AbbVie, and Janssen. M.C. has received research and travel grants for his institution from ViiV and Gilead. T.K. has received honoraria from Gilead Sciences and Roche Diagnostics. R.D.K. has received grants from the Swiss National Science Foundation and personal fees from Gilead Sciences, outside the submitted work. The remaining authors have no conflicts of interest to disclose.

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Received November 19, 2018

Accepted March 27, 2019

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