ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions

Authors

Rikke Olesen, University of North Carolina at Chapel Hill
Michael D. Swanson, University of North Carolina at Chapel Hill
Martina Kovarova, University of North Carolina at Chapel Hill
Tomonori Nochi, University of North Carolina at Chapel Hill
Morgan Chateau, University of North Carolina at Chapel Hill
Jenna B. Honeycutt, University of North Carolina at Chapel Hill
Julie M. Long, University of North Carolina at Chapel Hill
Paul W. Denton, University of Nebraska at OmahaFollow
Michael G. Hudgens, University of North Carolina at Chapel Hill
Amy Richardson, University of North Carolina at Chapel Hill
Martin Tolstrup, University of North Carolina at Chapel Hill
Lars Østergaard, University of North Carolina at Chapel Hill
Angela Wahl, University of North Carolina at Chapel Hill
J. Victor Garcia, University of North Carolina at Chapel Hill

Author ORCID Identifier

Paul W. Denton

Document Type

Article

Publication Date

2-8-2016

Publication Title

J. Clin Invest.

Volume

126

Issue

3

First Page

892

Last Page

904

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.

Comments

https://doi.org/10.1172/JCI64212

Recommended Citation

Olesen, Rikke; Swanson, Michael D.; Kovarova, Martina; Nochi, Tomonori; Chateau, Morgan; Honeycutt, Jenna B.; Long, Julie M.; Denton, Paul W.; Hudgens, Michael G.; Richardson, Amy; Tolstrup, Martin; Østergaard, Lars; Wahl, Angela; and Garcia, J. Victor, "ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions" (2016). Biology Faculty Publications. 134.
https://digitalcommons.unomaha.edu/biofacpub/134