Using HIV-1 sequence variability to explore virus biology.

Transmission of HIV requires a sufficiently infectious HIV carrier and a susceptible host. The parameter most closely associated with the sexual transmission of HIV is the viral concentration generally measured in serum or plasma as a surrogate for genital tract secretions. In their landmark study investigators working in the Rakai District of Uganda demonstrated that HIV transmission was very unlikely to occur when the concentration in blood fell below 3000 copies/mL blood. We developed assays to detect HIV in semen and collected a large number of specimens so as to accurately model the relationship between the concentration of HIV in semen and transmission probability. Shown in Figure 1 are the results of a probabilistic model built on measurement of HIV concentration in semen and the number of endocervical CCR5 receptors. The results of this model agree quite closely with empiric data available. The most contagious subjects would be expected to have the greatest concentration of HIV in genital secretions. Increased viremia is observed under 3 circumstances: 1) during the first days of infection when "ramp up viremia" is observed before host defenses such as antibodies and cell-mediated immunity can reduce viral replication; 2) when patients with acute or established HIV harbor concomitant "classic" STD pathogens; and 3) in the last stages of HIV disease when AIDS develops but people remain sexually active. (excerpt)

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Thomas Parran Award Lecture: transmission and prevention of transmission of HIV-1.

Biologic approaches to the prevention of sexual transmission of human immunodeficiency virus

This chapter describes various aspects of HIV transmission as well as antiretroviral therapy (ART) as prophylaxis. HIV transmission depends on the infectiousness of the host and the susceptibility of the partner. HIV in blood serves as a surrogate for the HIV in mucosal secretions to which the susceptible hosts are exposed. HIV concentrations in genital and rectal secretions show a high degree of correlation with the concentration of HIV in blood. Comparison of the concentration of HIV in semen with clinical trial results led to the development of a probabilistic model of male-to-female HIV transmission. The stage of HIV infection may also help define the probability of transmission. ART can be used to prevent sexual transmission of HIV in two ways: to reduce infectiousness and as pre-exposure or postexposure prophylaxis. The success of each strategy depends on the pharmacology and biology of the antiviral agents that are employed. The ability of antiretroviral agents to penetrate the genital tract is of central importance to the use of ART and the selection of the most appropriate antiviral agents. Three lines of evidence suggest that ART can be used for HIV prophylaxis: (1) animal studies, (2) human studies of prophylaxis to prevent vertical transmission of HIV, and (3) prophylaxis after needlestick injury.

F. Seillier

Papers

Effects of Genital Tract Inflammation on HIV-1 V3 Populations in Blood and Semen