Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061)

• Type of Material: Article
• Authors: Iris Chen, Johns Hopkins University; Gordon Chau, Fred Hutchinson Cancer Research Center; Jing Wang, Fred Hutchinson Cancer Research Center; William Clarke, Johns Hopkins University; Mark A. Marzinke, Johns Hopkins University; Vanessa Cummings, Johns Hopkins University; Autumn Breaud, Johns Hopkins University; Oliver Laeyendecker, National Institutes of Health; Sheldon D. Fields, Charles R. Drew University of Medicine and Science; Sam Griffith, Science Facilitation Department; Hyman M Scott, San Francisco Department of Public Health; Steven Shoptaw, University of California Los Angeles; Carlos Del Rio, Emory University; Manya Magnus, George Washington University; Sharon Mannheimer, Columbia University; Hong-Van Tieu, New York Blood Center; Darrell P. Wheeler, State University of New York at Albany; Kenneth H. Mayer, Harvard University; Beryl A. Koblin, New York Blood Center; Susan H. Eshleman, Johns Hopkins University
• Language: English
• Date: 2016-12-09
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0167629
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 12
• Start Page: e0167629
• End Page: e0167629
• Grant/Funding Information: National Institute of Allergy and Infectious Diseases to Oliver Laeyendecker.; National Institutes of Health R01-AI095068 to Susan H. Eshleman.; National Institutes of Health UM1-AI068613 to Susan H. Eshleman.
• Keywords: GAG; Science & Technology - Other Topics; GENETIC DIVERSITY; Multidisciplinary Sciences; VIREMIA; ENV; EVOLUTION; Science & Technology; SEQUENCE DIVERSITY; RESOLUTION MELTING ASSAY
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

Background: HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. Methods: A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits. Results: Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment. Conclusions: HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.