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 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
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
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
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.