Levels of HIV-1 RNA in genital secretions predict risk for heterosexual transmission of virus

Issue: May 2011

Higher concentrations of genital HIV-1 RNA concentrations are associated with a greater risk for heterosexual HIV-1 transmission, independent of plasma HIV-1 concentrations, according to a study.

In this prospective study, researchers enrolled 2,521 African HIV-1 serodiscordant couples, most of whom were married and cohabitating. “Ninety percent of new HIV-1 infections worldwide are transmitted sexually,” wrote Jared M. Baeten, MD, assistant professor of global health and medicine, division of allergy and infectious diseases, University of Washington, Seattle, and colleagues. “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.”

The median age for HIV-1-infected partners was 32 years; the median age for HIV-1-uninfected partners was 34 years. The median monthly frequency of intercourse was four times, with 28.6% of couples reporting having had unprotected sex during the month before enrollment in the study. Transmission of the virus within couples was established by viral sequence analysis.

Researchers tested endocervical samples from 1,805 of the women enrolled, including 46 of whom transmitted the virus to their partner. Semen samples were collected from 716 men enrolled in the study, including 32 who transmitted HIV-1 to their partner. The Spearman’s rank correlation coefficient was 0.56 for endocervical swabs; for semen, it was 0.55. Each 1.0 log10 increase in genital HIV-1 RNA was linked with a 2.20-fold increased risk for HIV-1 transmission in endocervical swabs (95% CI, 1.6-3.04) and a 1.79-fold risk for semen samples (95% CI, 1.3-2.47).

After adjusting for plasma HIV-1 quantity (HR=1.67, endocervical; HR=1.68, semen), genital HIV-1 RNA independently predicted HIV-1 transmission risk. There was less than a 1% incidence rate per year (seven female-to-male and four male-to-female) of HIV-1 transmissions from those with detectable plasma HIV-1 RNA, but undetectable genital HIV-1 RNA.

“These data suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk,” the researchers wrote.

A limitation noted in the study was that some of the HIV-1 transmission events “occurred before or several months after” the genital samples were collected. “However, the median time from acquiring the genital sample to HIV-1 seroconversion was less than 6 months, and for most HIV-1 transmission events, the genital sample was collected before or at the time of seroconversion.”

“Curiously, only the effect on female-to-male-transmission was statistically significant. This finding highlights the utility of focusing on the most proximal site where transmission occurs,” wrote Peter A. Anton, MD, director of the Center for Prevention Research at UCLA and a member of the UCLA AIDS Institute, and Betsy C. Herold, MD, professor of pediatrics, microbiology and immunology, and of obstetrics and gynecology and women’s health, at Albert Einstein College of Medicine. “The ‘discrepancy’ may also be attributed to sexual behaviors that were not captured in the study, including encounters with other partners. Notably, 40% of transmissions did not demonstrate linkage by viral sequences and likely reflect out-of-partnership exposures and infection. In addition, the study did not address receptive anal intercourse, which is being increasingly recognized among heterosexual couplings and is associated with a greater risk of HIV-1 infection.”

For more information:

Anton P. Sci Transl Med. 2011:doi:10.1126/scitranslmed.3002329.
Baeten JM. Sci Transl Med. 2011;doi:10.1126/scitranslmed.3001888.

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