Community-wide treatment of curable sexually transmitted diseases (STDs) reduced STD rates, and improved pregnancy outcomes, but did not reduce new HIV infections, in a recent study supported by the National Institute of Allergy and Infectious Diseases (NIAID). The study was conducted in a rural region of Uganda where STDs and HIV infection are common.
Numerous epidemiological studies suggest that people with STDs have a greatly increased risk for HIV infection," explains Maria Wawer, M.D., one of the principal investigators on the study. "We conducted a controlled trial to see if community-wide treatment of curable STDs might reduce HIV infection rates." Dr. Wawer, an NIAID grantee at the Columbia University School of Public Health in New York City, presented results of the study on July 3, 1998, at the 12th World AIDS Conference in Geneva, Switzerland.
Dr. Wawer and a team of researchers from Uganda and the United States began the study, known as the Rakai STD Control for AIDS Prevention Study, in 1994. The scientists conducted the study in 56 villages in Uganda's Rakai district, where approximately 16 percent of the population is infected with HIV. STDs also are highly prevalent in Rakai. At baseline, for example, approximately 10 percent of the population had evidence of having had syphilis, while bacterial vaginosis and trichomoniasis affected about one-half and one-fourth, respectively, of all women. The prevalence of gonorrhea and chlamydial infections were about 2 and 4 percent, respectively.
The researchers randomly assigned groups of villages to either the intervention or comparison arms of the study. In the intervention arm, 6,602 HIV-negative adults between the ages of 15 and 59 received home-based, observed, antibiotic treatment against a broad range of STDs, whether or not they had symptoms. A total of 6,124 HIV-negative adults in the comparison arm were treated in the home for parasitic worm infections and given nutritional supplements.
Home-based treatments in both the intervention and comparison groups were repeated every 10 months, at which time all participants were screened for STDs and tested for HIV infection. Anyone in the comparison group who had STD symptoms at the time of the in-home study visits was referred to local project clinics for standard Ugandan STD treatment. All study participants were instructed to seek treatment at local clinics, which offered the prevailing standard of care, if they experienced STD symptoms in-between the visits of the research teams.
After the second 10-month follow-up, an analysis of study data showed that the treatment for curable STDs had had no effect on HIV incidence, i.e., the rate of new HIV infections was the same in the intervention and comparison groups. In fact, HIV infection rates increased slightly in both groups during the study. On the other hand, the STD treatment regimen did reduce the prevalence of most targeted STDs. Syphilis and trichomoniasis were significantly reduced in the intervention group relative to the comparison group at follow-up. Among pregnant women enrolled in the study, rate of gonorrhea, chlamydia, trichomoniasis and bacterial vaginosis were significantly lower in the intervention group than the comparison group at follow-up. The rate of new HIV infections among pregnant women, however, was the same in the intervention and comparison groups.
The Rakai findings contrast with the only other completed community-based study that examined whether STD treatment can reduce the rate of HIV infection. In 1995, scientists reported results of a study conducted in the Mwanza region of Tanzania in which entire communities received either clinic-based treatment of symptomatic STD infections or the existing standard of care. This region was in a much earlier phase of the HIV epidemic compared to Rakai - only about 4 percent of the population was infected with HIV at the time of the study. Although the Mwanza study showed only limited effects of the intervention on STD rates, the rate of new HIV infections was 38 percent lower in the intervention group compared with the control group.
In Rakai, STDs are associated with increased risk of HIV transmission in individuals," explains co-principal investigator Ronald Gray, M.D., of Johns Hopkins University in Baltimore, Md. "There is also a substantial background risk of exposure to HIV, irrespective of concurrent STDs. Thus, STDs may have contributed little to overall HIV transmission in this population, indicating that differences in the stage of the HIV epidemic may be important in this regard". "The Rakai findings underscore the vital need for additional research in this area," adds Penelope J. Hitchcock, D.V.M., chief of NIAID's sexually transmitted diseases branch. "Additional trials conducted in populations in which the epidemic is beginning will help determine the role of STD control in preventing HIV transmission. Studies to determine the importance of genital herpes and bacterial vaginosis in HIV transmission are also needed." Nelson Sewankambo, MB.ChB., the Ugandan principal investigator of the current study, from Makerere University, Kampala, stressed the importance of study findings with respect to the impact on STDs. "The mass treatment intervention substantially reduced STDs among pregnant women, and resulted in marked improvement in maternal and infant health," he noted. "These findings could help define new strategies for STD control in pregnancy."
Scientists from Makerere University, Kampala; Johns Hopkins University in Baltimore; and the Uganda Virus Institute of the Uganda Ministry of Health collaborated with Drs. Wawer, Gray and Sewankambo on the study. In addition to NIAID, the National Institute of Child Health and Human Development (NICHD), the Rockefeller Foundation and the World Bank Uganda STI Project provided support for this study.
Press releases, fact sheets and other NIAID-related materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov. The home page for the 12th World AIDS Conference is http://www.aids98.ch.