A large clinical trial in a Ugandan population heavily infected with the human immunodeficiency virus (HIV) has shown that despite reductions in sexually transmitted diseases (STDs), HIV incidence was not reduced by STD control measures. The findings, by scientists from Makerere University in Uganda, the Johns Hopkins School of Public Health, and the Columbia University School of Public Health contradicted those of an earlier study in Mwanza, Tanzania, which found that the rate of HIV infection was 38 percent lower after symptomatic STDs were treated in clinics. The report appeared in the February 13 issue of The Lancet.
Although scientists have long suspected an association between HIV and STDs, the connection remains elusive. Senior author Ronald H. Gray, professor, Population and Family Health Sciences, Johns Hopkins School of Public Health, said, "Given the significant impact that our mass treatment campaign in Uganda had on STDs, it's disappointing to find no differences in HIV incidence between the treated and untreated populations."
The study, which enrolled a total of 15,127 HIV-negative subjects, was conducted in Rakai District, a rural region in southwestern Uganda with a high prevalence of HIV infection (15.9 percent). In the intervention arm of the trial, the scientists brought an intensive STD control strategy into participants' homes and provided entire communities with broad-spectrum antibiotic treatment for STDs ("mass treatment"). Control-arm subjects received mass treatment with vitamin and iron supplements and worm medication. Control-arm subjects whose blood tests revealed syphilis, or who reported current STD symptoms during the interviews, were referred during the 10-monthly visits for free treatment provided by the project itself.
At follow-up after mass STD treatment, the prevalences of syphilis and trichomonas were lower in the intervention arm compared to the control arm. In pregnant women, trichomonas, bacterial vaginosis, chlamydia, and gonorrhea were all significantly reduced in those receiving the STD treatment. Despite these significant differences in STD rates realized between study arms, STD control had no effect on HIV incidence, and HIV incidence was especially high in pregnant women. This is in contrast to the trial in Mwanza, Tanzania.
The scientists think it unlikely that problems in study design or follow-up account for the failure to lower HIV incidence in the Rakai district. Treatment coverage was high. Over 80 percent of all eligible adults in the communities (and over 90 percent of those enrolled) accepted treatment. The researchers felt that the fact that STD services were offered to symptomatic control subjects at ten-month intervals could not explain the absence of any effect on HIV, since relatively few symptomatic persons used these services.
Dr. Gray said, "Our data show that STDs increase the risk of HIV infections at an individual level, but with the high background prevalence of HIV, most HIV transmission occurs independently of STD transmission."
The earlier Mwanza trial involved a population with a low-grade HIV epidemic (infection rate of 4.1 percent), whereas the epidemic in Rakai was "mature" and generalized, with 15.9 percent of the population HIV-positive.
First author Maria Wawer, MD, MSH, Columbia University, and adjunct associate professor, Johns Hopkins University, said, "This trial raises important questions with regard to future policies on STD control and HIV prevention and, thus, it is imperative to determine whether the divergent findings between our trial and the one in Mwanza reflect differences in the stage of the two HIV epidemics." Wawer described ongoing collaborative reassessment by the two research teams, and advocated new trials in regions where HIV incidence is high and where it is low. Nelson Sewankambo, MBChB, dean of medicine, Makerere University, and the Ugandan principal investigator, noted that "irrespective of the impact on HIV, this trial demonstrated important reductions in STDs and health benefits, particularly for women and their children."
The study was supported by grants from the National Institute of Allergy and Infectious Diseases; the National Institute of Child Health and Development; the U.S. National Institutes of Health; the Rockefeller Foundation; and the World Bank Uganda STI Project and John Snow Inc.
Journal
The Lancet