ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions
Year: 2016
Type: article
Abstract: The recently completed HIV prevention trials network study 052 is a landmark collaboration demonstrating that HIV transmission in discordant couples can be dramatically reduced by treating the infected individual with antiretroviral therapy (ART). However, the cellular and virological events that occur in the female reproductive tract (FRT) during ART that result in such a drastic decrease in transmission were not studied and remain unknown. Here, we implemented an in vivo model of ART in BM/liver/thymus (BLT) humanized mice in order to better understand the ability of ART to prevent secondary HIV transmission. We demonstrated that the entire FRT of BLT mice is reconstituted with human CD4+ cells that are shed into cervicovaginal secretions (CVS). A high percentage of the CD4+ T cells in the FRT and CVS expressed CCR5 and therefore are potential HIV target cells. Infection with HIV increased the numbers of CD4+ and CD8+ T cells in CVS of BLT mice. Furthermore, HIV was present in CVS during infection. Finally, we evaluated the effect of ART on HIV levels in the FRT and CVS and demonstrated that ART can efficiently suppress cell-free HIV-RNA in CVS, despite residual levels of HIV-RNA+ cells in both the FRT and CVS.
DOI: 10.1172/jci64212
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: National Institutes of Health, Center for AIDS Research, University of Washington, Japan Society for the Promotion of Science, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, Center for AIDS Research, University of North Carolina at Chapel Hill
Awards: Mechanisms of Cell-associated HIV Transmission in Humanized Mice, G1467100060, Prevention of HIV Acquisition by Long-acting Antiretroviral PrEP, Development of novel technology for prevention of mastitis using nanotechnology, G2230551448, Plug & Purge: In Vivo Targeting of Active HIV Reservoirs That Persist Despite ART, Elucidation of molecular mechanism that promotes IgA production in the mammary gland, G4245712776, Integrated Training in Cancer Model Systems, Basic Immune Mechanisms, G6027102683, G6163189475, G8541996175, G8590368283, G8809002381, G9000075494, UNC Center for Environmental Health and Susceptibility, The University of North Carolina Center for AIDS Research
OpenAlex ID: W2266944971