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Genital Viral Load Predicts Heterosexual HIV Transmission Risk

Higher levels of HIV RNA in semen or female genital fluids are associated with a greater likelihood of HIV transmission during sex.

Prior research has shown that people with undetectable blood plasma HIV viral load have a lower risk of transmitting the virus to sexual partners or from mother to baby.

Plasma and genital fluid HIV RNA levels are related, but some individuals have detectable virus in their blood but not their genital fluids, or vice versa. However, the direct correlation between genital HIV levels and sexual transmission risk has not been well studied.

In the present study, described in the April 6, 2011, issue of Science Translational Medicine, Jared Baeten from the University of Washington and colleagues looked at the link between genital HIV RNA levels and transmission risk.

This prospective analysis included 2521 serodiscordant (1 HIV positive, the other negative) heterosexual couples in 7 African countries (Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, and Zambia).

Participants underwent HIV testing and received prevention counseling every 3 months. The researchers tested cervical fluid swab samples from 1805 women and semen samples from 716 men. In cases of new HIV infection, viral sequencing was performed to determine if the initially negative member of a couple was infected by his or her steady partner.

Results

• 46 of the 1805 women tested transmitted HIV to their male partner.
• 32 of the 716 men tested transmitted the virus to their female partner.
• Overall, there was a positive correlation between genital fluid and plasma HIV RNA concentrations:
• For cervical samples, Spearman's rank correlation coefficient -- a statistical measure of correlation -- was 0.56, indicating a strong relationship;
• For semen samples, the coefficient was similar, at 0.55.
• Each 1 log increase in cervical fluid HIV RNA was associated with a 2.2-fold higher risk of transmission.
• Each 1 log increase in semen viral load was associated with a 1.79-fold higher transmission risk.
• Genital fluid viral load still independently predicted HIV transmission risk after adjusting for plasma viral load (hazard ratio 1.67 for cervical fluid and 1.68 for semen).
• 7 cases of female-to-male transmission and 4 instances of male-to-female transmission occurred from people with undetectable genital fluid viral load, an incidence of <1% per year.
• In all 11 cases, however, the transmitted partner did have detectable plasma viral load.

Thus, the study authors concluded, "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, they added, "suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk."

Although uncommon, however, the 11 cases of transmission with undetectable genital viral load indicate that plasma viral load is also an important consideration.

Investigator affiliations: Department of Global Health, Department of Medicine, Department of Epidemiology, Department of Pediatrics, and Department of Laboratory Medicine, University of Washington, Seattle, WA; Wits Institute for Reproductive Health and HIV, University of the Witwatersrand, Johannesburg 2001, South Africa; Department of Epidemiology and Biostatistics, Makerere University, Kampala, Uganda; Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya; Vaccine and Infectious Disease Institute and Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA.

4/12/11

Reference

JM Baeten, E Kahle, JR Lingappa, et al. Genital HIV-1 RNA Predicts Risk of Heterosexual HIV-1 Transmission. Science Translational Medicine 3(77): 77ra29 (abstract). April 6, 2011.

P Anton and BC Herold. HIV Transmission: Time for Translational Studies to Bridge the Gap (Perspective). Science Translational Medicine 3(77): 77ps11 (abstract). April 6, 2011.

Other Source
AAAS. Genital Samples Reveal HIV Transmission Risk. Media advisory for April 6, 2011.