The HIV Reservoir in the Female Reproductive Tract

Antiretrovirals can prevent the spread of replicating HIV within the host and decrease the virus in plasma to levels undetectable in clinical assays, and in genital secretions to untransmissible levels. However, during effective treatment with antiretrovirals, infectious HIV persists lifelong because the virus integrates into the host's DNA, and these proviruses are replicated within the host's DNA when the infected host cells proliferate. Cells with infectious virus that persist during antiretroviral therapy (ART), the HIV reservoir, are spread throughout the body, including the female reproductive tract (FRT). HIV-infected cells have been detected at multiple sites in the FRT, and the virus is shed in FRT secretions; however, less is known about the FRT reservoir than about other sites in the body. The FRT consists of the ovaries, fallopian tubes, uterus, cervix, and vagina. This collection of diverse tissues has several unique features: squamous and columnar epithelia, hormone production and regulation, cyclical changes, a unique microbiome, and exposure to sexual activity. Given these unique features, it cannot be assumed that infected cells located in the FRT will respond to curative therapeutic interventions in the same manner as infected cells elsewhere in the body. Thus, it is imperative to increase our understanding of the features of the HIV reservoir in the FRT. Here, we review data on the viral reservoir and shedding in the FRT and relate it to strategies to cure HIV infection.