Journal
MUCOSAL IMMUNOLOGY
Volume 9, Issue 3, Pages 821-833Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2015.145
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Funding
- National Institute of Allergy and infectious Disease (NIAID), the National Institutes of Health (NIH) [AI51794, AI104387, AI115981, AI116086]
- CONRAD (USAID) [GP00-08-00005-00, PPA-09-046]
- National Research Foundation [67385]
- Medical Research Council of South Africa
- Technology Innovation Agency
- Columbia University-Southern African Fogarty AIDS International Training and Research Program (AITRP) - Fogarty International Center, NIH [D43TW00231]
- Medical Research Council of South Africa Self-Initiated Grant (MRC SIR)
- National Research Foundation (NRF) of South Africa
- NIH NIAID HVTN Laboratory Center [UM1AI068618]
- NIH NIAID Duke Center for AIDS Research Immunology Core [P30 AI 64518]
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The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisition in women assigned to tenofovir gel (n = 24) and placebo gel (n = 24) in the CAPRISA 004 microbicide trial to assess if this topical antiretroviral had an impact on mucosal and systemic antibody responses. Linear mixed effect modeling and partial least squares discriminant analysis was used to identify multivariate antibody signatures associated with tenofovir use. There were significantly higher response rates to gp120 Env (P = 0.03), p24 (P = 0.002), and p66 (P = 0.009) in plasma and GT in women assigned to tenofovir than placebo gel at multiple time points post infection. Notably, p66 IgA titers in the GT and plasma were significantly higher in the tenofovir compared with the placebo arm (P<0.05). Plasma titers for 9 of the 10 HIV-IgG specificities predicted GT levels. Taken together, these data suggest that humoral immune responses are increased in blood and GT of individuals who acquire HIV infection in the presence of tenofovir gel.
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