Low Blood Levels of HIV Reduce Risk of Heterosexual Transmission

The lower the level of HIV in the blood, the less likely infected persons will transmit the virus to heterosexual partners, according to a study in Africa supported by the National Institutes of Health (NIH). In this week's New England Journal of Medicine, an international team reports results of the largest survey ever to examine the link between the concentration of virus in a person's blood-known as viral load-and other risk factors for HIV heterosexual transmission. The findings suggest viral load is the most important predictor of HIV transmission between men and women, regardless of the gender of the transmitting individual.

The two-and-a-half-year survey followed more than 400 heterosexual couples, in each of which only one person was HIV-positive. The study found that the more virus individuals carried, the more likely they were to infect their sexual partners. Conversely, no one who had fewer than 1,500 copies of HIV per milliliter (ml) of blood transmitted the virus to his or her partner.

"The findings uphold the strategic benefit of lowering levels of HIV in the blood," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), which supported the study. "This research lends hope that even if HIV cannot be eradicated from the body, antiretroviral drugs or vaccines may help reduce heterosexual transmission of HIV, the predominant way AIDS is spreading in Africa and many parts of the world."

The study, co-funded by the National Institute of Child Health and Human Development (NICHD), took place in Uganda's rural Rakai district. Ugandan researchers from Makerere University in Kampala and the Uganda Virus Research Institute/Ministry of Health in Entebbe collaborated with U.S. colleagues from Johns Hopkins University, Columbia University and NIH. The article's senior author, Thomas C. Quinn, M.D., is professor of medicine at Hopkins and senior investigator in NIAID's Laboratory of Immunoregulation.

Dr. Quinn and his colleagues set out to better define risk factors associated with heterosexual transmission. "Viral load was the critical factor among the couples in our study," he explains. "We observed a clear dose response. With every 10-fold rise in the concentration of HIV in the bloodstream, transmission more than doubled."

The study prospectively followed 415 HIV-discordant couples-228 HIV-positive men and 187 HIV-positive women and their HIV-negative, long-term sexual partners-who were participating in the Rakai Project, a larger trial of HIV prevention. All the couples received free condoms, voluntary confidential HIV testing and counseling, treatment, and health education directed at preventing HIV transmission. In this remote district of Uganda, anti-HIV drugs are not available.

The research team visited the couples at 10-month intervals for up to 30 months, conducting private, same-sex interviews. Researchers assessed a variety of factors, such as behaviors (for example, condom use, number of sexual partners and frequency of intercourse), general health history, AIDS-defining symptoms or conditions, and circumcision status. Study volunteers also gave blood and urine samples, and women provided self-collected vaginal swabs for evaluation of HIV and sexually transmitted diseases.

Individuals were privately notified of test results during the study and encouraged to share their HIV status with their partners. Despite provision of condoms, HIV testing and counseling, and health education, 90 (22 percent) of the previously uninfected partners became HIV-positive.

Using blood samples archived from each study visit, the scientists later determined HIV viral loads using polymerase chain reaction assays. They found higher viral load correlated with higher rates of HIV transmission. Nearly 80 percent of the cases of new infections resulted from exposure to HIV-positive partners with more than 10,000 copies of HIV per ml of blood.

"Our findings are strikingly consistent with results from studies of viral load in cases of mother-to-child HIV infection," notes Dr. Quinn. "Theoretically, just as drugs have helped reduce perinatal transmission, antiretroviral regimens that dampen HIV viral load should also be effective against heterosexual transmission of HIV. But we need more studies to confirm this."

Antiretroviral therapy is seen primarily as a benefit to the HIV-infected individual, say the study's co-principal investigators, Maria J. Wawer, M.D., of Columbia and Ronald H. Gray, M.D., of Hopkins; however, the new results suggest that measures to reduce viral load may provide a means of controlling the epidemic, they comment. Similarly, Ugandan principal investigator Nelson Sewankambo, M.D., dean of medicine at Makerere University, notes the need to develop low-cost and feasible methods of reducing viral load for use in resource-poor settings.

Along with viral load, the team also examined several other important variables for risk of HIV transmission. Overall, they found no statistical difference in the rate of transmission from male to female compared with female to male. However, circumcision in the male was significantly associated with decreased HIV acquisition. In addition, younger couples (aged 15 to 19 years) experienced the highest rates of seroconversion.

"The Rakai Project is the most comprehensive survey of heterosexual transmission in Africa, where the HIV epidemic has hit the hardest," says project officer Rod Hoff, D.Sc., with NIAID's Division of AIDS. "This team's study is remarkable for its scope and quality of science, and it points the way for developing new interventions to prevent HIV transmission."

NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NICHD supports and conducts research on the reproductive, neurobiological, developmental and behavioral processes that determine and maintain the health of children, adults, families and populations. NIAID and NICHD are components of the NIH, an agency of the U.S. Department of Health and Human Services.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov. References: T Quinn et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. New England Journal of Medicine 342(13): 921-29 (2000).