OA18.05
Background: All mucosal exposures to HIV occur in the presence of semen. Currently, there is no consensus on the effect of semen on HIV transmission or on the potential effectiveness of topical microbicides. Here, we use an in vivo animal model of mucosal HIV transmission to establish the effect of semen on vaginal HIV infection and on the efficacy of topical microbicides.
Methods: We utilized bone marrow/liver/thymus (BLT) humanized mice; a model validated for the study of vaginal HIV transmission and HIV prevention strategies. We first evaluated the transmission of transmitted/founder viruses in the presence or absence of human semen. In addition, we also evaluated the effect of semen on cell-associated HIV transmission. Lastly, we evaluated the efficacy of topically applied microbicides in the presence of semen using the CCR5 antagonist, maraviroc. Log rank Mantel-Cox was used to analyze the data.
Results: To determine the effect of semen on vaginal transmission HIV-1CH040, a transmitted founder (T/F) virus, was resuspended in human semen and vaginally administered to BLT mice. Efficient transmission was observed regardless of the presence (6/6) or absence (4/4) of semen. No differences were noted in the levels of peripheral viral load or CD4+ T cell decline between the two groups. When cell-associated HIV was used for challenge in the presence of semen, 3/4 BLT mice became infected compared to 4/4 in the control arm. When animals were treated vaginally with maraviroc and then challenged with HIV in semen, complete protection was observed (6/6).
Conclusions: Our results demonstrate that semen does not enhance transmission of either cell-free or cell-associated HIV. In addition, semen does not diminish the protective effect of maravioc from vaginal HIV infection when applied topically. Our results establish a new paradigm for the evaluation of HIV prevention strategies that includes human semen in the context of cell-free and cell-associated virus.
