Monthly prophylactic treatment of female sex workers in Kenya with the antibiotic azithromycin fails to reduce the incidence of HIV-1 infection despite reducing the incidence of other sexually transmitted infections (STIs), according to findings from a randomised controlled trial published in the June 2nd edition of the Journal of the American Medical Association.
STIs are important co-factors in the spread of HIV. Not only can STIs enhance the sexual transmission of HIV by increasing the rate of viral shedding, but HIV infection can also increase susceptibility to STIs. Previous studies examining the effect of antibiotic treatment of sexually transmitted infections on HIV infection within African communities have produced mixed findings. This study was designed to assess whether prophylactic antibiotic treatment affects the rate of HIV transmission among female sex workers, a group who are at a high risk of contracting STIs.
The investigators recruited 466 HIV-negative female sex workers from the Kibera area of Nairobi between May 1998 and January 2002. The participants were randomised to receive either 1g of azithromycin or placebo once a month. The two groups were similar in terms of demographic characteristics, sexual activity, drug and alcohol use, and prevalence of STIs at baseline.
Monthly urine samples and three-monthly cervical swabs and blood samples were tested for Neisseria gonorrheae, Chlamydia trachomatis, Trichomonas vaginalis, syphilis, bacterial vaginosis, Lactobacillus and Candida. At the three-monthly visits, the women were also asked about numbers of clients, consistency of condom use and types of sexual activity, and were tested for HIV infection. All participants received regular counselling on HIV prevention, free male condoms, and treatment for any STIs discovered.
Three hundred and forty-one women (73%) were followed up for over two years. There were no differences in the incidence of HIV infection between the treatment and placebo arms (4.0% vs. 3.2%; p = 0.5).
The women treated with azithromycin had reduced rates of infection with N. gonorrheae (rate ratio [RR] = 0.46; 95% confidence interval [CI], 0.31 – 0.68), C. trachomatis (RR = 0.38, 95% CI, 0.26 – 0.57), and T. vaginalis (RR = 0.56, 95% CI, 0.40 – 0.78). Treatment with azithromycin did not affect the incidence of bacterial vaginosis, syphilis, Candida or Lactobacillus.
Despite these findings, HIV infection was more common in women who had been infected with N. gonorrheae (RR = 4.9; 95% CI, 1.7 – 14.3) or C. trachomatis (RR = 3.0; 95% CI, 1.1 – 8.9). “Incident HIV-1 infection was strongly associated with both N. gonorrheae and C. trachomatis over the preceding three months, confirming the association between HIV-1 and a prior STI,” state the authors. “However, the observed failure of monthly prophylaxis to protect against HIV-1 acquisition was not due to a failure to prevent bacterial STIs.”
The authors offer a number of explanations for this apparent discrepancy. Firstly, the women in this study were receiving higher standards of screening and care than normal for the study region, possibly reducing the number of HIV infections that could be attributed to STIs.
They also propose that other pathways may account for the observed association between HIV infection and the presence of STIs, including increased viral shedding in male clients with STIs, or a high prevalence of STIs amongst HIV-positive men. This would lead to female sex workers being exposed to high levels of both HIV and other STIs, but without STI treatment reducing the risk of HIV infection.
Alternatively, the women could be more susceptible to STIs after acute HIV infection. In this study, the women were tested every month for STIs but only every three months for HIV. It is possible, then, that STIs could have been contracted and treated before HIV seroconversion had been detected.
At the end of the study, the investigators tested the women’s frozen plasma samples for the presence of herpes simplex virus 2 (HSV-2). At baseline, 73% of the participants were infected with HSV-2, and these women were more likely to become infected with HIV during follow-up (RR = 6.3; 95% CI, 1.5 – 27.1).
Since the study was not designed to assess the role of HSV infection on acquisition of HIV, the authors point out that it is not possible to ascertain whether prior HSV infection increased the chances of contracting HIV, or an unexamined factor increased the susceptibility to both HSV and HIV.
“The findings confirm the association between HSV-2 infection and HIV-1 acquisition,” conclude the authors, “and provide a strong rationale for current trials of HSV-2 suppression as an HIV-1 prevention strategy in Africa.”
Reference
Kaul R et al. Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers. JAMA 291: 2555-2562, 2004.