Quantifying Ongoing HIV-1 Exposure in HIV-1-Serodiscordant Couples to Identify Individuals With Potential Host Resistance to HIV-1.

TitleQuantifying Ongoing HIV-1 Exposure in HIV-1-Serodiscordant Couples to Identify Individuals With Potential Host Resistance to HIV-1.
Publication TypeJournal Article
Year of Publication2012
AuthorsMackelprang RD, Baeten JM, Donnell D, Celum C, Farquhar C, de Bruyn G, Essex M, McElrath JM, Nakku-Joloba E, Lingappa JR
Corporate Authorsfor the Partners in Prevention HSV/HIV Transmission Study Team
JournalJ Infect Dis
Volume206
Issue8
Pagination1299-1308
Date Published2012 Oct
ISSN1537-6613
Abstract

Background. Immunogenetic correlates of resistance to HIV-1 in HIV-1-exposed seronegative (HESN) individuals with consistently high exposure may inform HIV-1 prevention strategies. We developed a novel approach for quantifying HIV-1 exposure to identify individuals remaining HIV-1 uninfected despite persistent high exposure. Methods. We used longitudinal predictors of HIV-1 transmission in HIV-1 serodiscordant couples to score HIV-1 exposure and define HESN clusters with persistently high, low, and decreasing risk trajectories. The model was validated in an independent cohort of serodiscordant couples. We describe a statistical tool that can be applied to other HESN cohorts to identify individuals with high exposure to HIV-1. Results. HIV-1 exposure was best quantified by frequency of unprotected sex with, plasma HIV-1 RNA levels among, and presence of genital ulcer disease among HIV-1-infected partners and by age, pregnancy status, herpes simplex virus 2 serostatus, and male circumcision status among HESN participants. Overall, 14% of HESN individuals persistently had high HIV-1 exposure and exhibited a declining incidence of HIV-1 infection over time. Conclusions. A minority of HESN individuals from HIV-1-discordant couples had persistent high HIV-1 exposure over time. Decreasing incidence of infection in this group suggests these individuals were selected for resistance to HIV-1 and may be most appropriate for identifying biological correlates of natural host resistance to HIV-1 infection.

DOI10.1093/infdis/jis480
Alternate JournalJ. Infect. Dis.
PubMed ID22926009