Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model

Objective: To develop a model to predict transmission of HIV-1 from men to women. Design: HIV-1 in seminal plasma, and endocervical CCR5 receptors were corre lated with epidemiological studies of HIV-1 transmission to develop a proba bilistic model. Settings: Semen samples were collected from patient subjects in Seattle Was hington, Chapel Hill, North Carolina, and St. Gallen, Switzerland. Endocerv ical biopsy specimens were obtained from women in Chicago, Illinois. Participants: Eighty-six men (not receiving antireroviral therapy) in whom CD4 cell count and semen volume were available, and 24 women in whom the nu mber of endocervical CCR5 receptors were determined. Main outcome measures: Prediction of transmission of HIV-1 from men to wome n per episode of vaginal intercourse based on the absolute burden of HIV (v olume x HIV RNA copies/ml seminal plasma). Results: The model suggests efficient heterosexual transmission of HIV-1 wh en semen viral burden is high. When semen contains 1 00 000 copies of non-s yncytium-inducing (NSI) HIV RNA the probability of HIV-1 transmission is 1 per 100 episodes of intercourse; conversely, with 1000 copies NSI HIV RNA i n semen, transmission probability is 3 per 10 000 episodes of intercourse. Conclusions: This model links biological and epidemiological data related t o heterosexual HIV-1 transmission. The model can be used to estimate transm ission of HIV from men with high semen viral burden from inflammation, or r educed burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier s tudies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategi es. (C) 2001 Lippincott Williams & Wilkins.