Genital HIV-1 RNA Predicts Risk of Heterosexual HIV-1 Transmission

Genital HIV-1 RNA quantity predicts risk of heterosexual HIV-1 transmission independently of plasma HIV-1 concentration. Elucidating the Insidious Transmission of a Deadly Pathogen The deadly HIV-1 retrovirus that causes AIDS has been a scourge of humanity for nearly 30 years. Although combination therapy with antiretroviral drugs has proved successful, the complex drug regimen and great cost have prevented their widespread use in the developing world where they are most needed. The goal of developing a vaccine that would protect individuals from becoming infected with HIV-1 has remained elusive. Given that 90% of all HIV infections worldwide are due to sexual transmission, there has been much interest in developing new strategies that could block HIV infection through the genital mucosa. However, the mechanisms underlying mucosal transmission of HIV are still poorly understood. Higher amounts of HIV-1 in genital secretions are thought to reflect a greater chance of sexual transmission, but testing this correlation is a difficult undertaking. Baeten and colleagues have taken on this challenge with their prospective study in Africa of 2521 heterosexual serodiscordant couples (one partner is HIV-infected and the other partner is not). These investigators evaluated the relationship between the quantity of HIV-1 RNA in the genital secretions of the infected partner and the risk of HIV-1 transmission to the uninfected partner in each couple. They tested the amount of HIV-1 RNA in endocervical swabs from 1805 HIV-1–infected women including 46 women known to have transmitted the virus to their male partners. They also tested the amount of HIV-1 RNA in semen from 716 men, including 32 who had transmitted HIV-1 to their female partners. The authors demonstrate that higher concentrations of HIV-1 RNA in genital secretions are associated with a greater risk of heterosexual transmission of HIV-1, and that these concentrations provide a new biomarker for predicting the infectiousness of HIV-1–infected individuals. The authors propose that HIV-1 RNA concentrations in genital secretions could also be used as a biomarker to monitor the efficacy of new microbicides and other interventions designed to block mucosal transmission of the virus. High plasma HIV-1 RNA concentrations are associated with an increased risk of HIV-1 transmission. Although plasma and genital HIV-1 RNA concentrations are correlated, no study has evaluated the relationship between genital HIV-1 RNA and the risk of heterosexual HIV-1 transmission. In a prospective study of 2521 African HIV-1 serodiscordant couples, we assessed genital HIV-1 RNA quantity and HIV-1 transmission risk. HIV-1 transmission linkage was established within the partnership by viral sequence analysis. We tested endocervical samples from 1805 women, including 46 who transmitted HIV-1 to their partner, and semen samples from 716 men, including 32 who transmitted HIV-1 to their partner. There was a correlation between genital and plasma HIV-1 RNA concentrations: For endocervical swabs, Spearman’s rank correlation coefficient ρ was 0.56, and for semen, ρ was 0.55. Each 1.0 log10 increase in genital HIV-1 RNA was associated with a 2.20-fold (for endocervical swabs: 95% confidence interval, 1.60 to 3.04) and a 1.79-fold (for semen: 95% confidence interval, 1.30 to 2.47) increased risk of HIV-1 transmission. Genital HIV-1 RNA independently predicted HIV-1 transmission risk after adjusting for plasma HIV-1 quantity (hazard ratio, 1.67 for endocervical swabs and 1.68 for semen). Seven female-to-male and four male-to-female HIV-1 transmissions (incidence <1% per year) occurred from persons with undetectable genital HIV-1 RNA, but in all 11 cases, plasma HIV-1 RNA was detected. Thus, higher genital HIV-1 RNA concentrations are associated with greater risk of heterosexual HIV-1 transmission, and this effect was independent of plasma HIV-1 concentrations. These data suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk.