SeriesControl of sexually transmitted diseases for HIV-1 prevention: understanding the implications of the Mwanza and Rakai trials
Introduction
The global burden of curable sexually transmitted diseases (STDs) is enormous, with an estimated total of more than 300 million new cases of syphilis, gonorrhoea, chlamydia, and trichomoniasis each year.1 Because of their many serious complications and sequelae, particularly among women, STDs are one of the leading causes for the loss of healthy years of life. Even in the absence of HIV-1 infection, STDs account for a larger number of disability-adjusted life-years lost in women of childbearing age than any other group of diseases apart from maternity-related disorders.2 Effective control of STDs was therefore a pressing global health priority even before their role as a cofactor in HIV-1 transmission was recognised.
During the past decade, overwhelming evidence has accumulated that some STDs enhance the transmission of HIV-1. Proving that STDs were indeed a cofactor was initially difficult, because HIV-1 and STDs share a mode of transmission, so associations seen in epidemiological studies may well have resulted from the confounding effect of risky sexual behaviour.3 Moreover, in cross-sectional studies, the time sequence of infections is difficult to establish. Longitudinal studies provided stronger evidence, and showed substantial relative risks for HIV-1 infection associated with various STDs.4, 5, 6, 7 Further evidence has come from studies showing that viral shedding in the genital tract of HIV-1-infected men and women is substantially increased if they have an STD, and that treatment of the STD decreases viral shedding.8, 9, 10
Towards the end of the 1980s, Pepin and colleagues11 suggested that STD control could be used as an indirect strategy to reduce HIV-1 transmission. On the basis of this hypothesis, WHO promoted improved STD treatment services, together with behavioural risk reduction, as essential components of national AIDS control programmes,12 and this strategy has since been adopted in many countries. However, the impact of this approach is difficult to predict because it depends on the size of the cofactor effect, the prevalence of STDs in HIV-1-discordant partners, the proportion of treatable compared with untreatable STDs, and the effectiveness of control measures in reducing STD prevalence, none of which are easy to estimate.
Two types of investigation have collected empirical evidence on the effectiveness of an STD control strategy for HIV-1 prevention: uncontrolled intervention studies among sex workers, and community-based randomised controlled trials in general populations. These studies were done in sub-Saharan Africa, the region most severely affected by the HIV-1 pandemic, and where high prevalences of treatable STDs have been recorded in many countries. In former Zaire and Côte d'Ivoire, the introduction of effective and accessible STD treatment services for sex workers, with condom promotion and provision, was followed by a substantial and significant reduction in STD and HIV-1 incidence.13, 14 The effects remained after adjusting for condom use in the analysis, but residual confounding cannot be excluded and it is therefore difficult to disaggregate the effects of STD treatment from those of condom use. A further study in a mining community in South Africa showed that monthly presumptive STD treatment of sex workers reduced the prevalence of STDs not only in this high risk group, but also in the surrounding population of miners.15 However, the effect on HIV-1 transmission was not measured directly in this study.
Section snippets
Mwanza
A randomised trial in Mwanza region, Tanzania (map), between 1991 and 1994, tested the hypothesis that improved treatment services for STDs, integrated within the existing primary health-care system, would reduce HIV-1 transmission in the general population.16, 17 The intervention comprised training of health workers in syndromic case management as recommended by WHO, provision of inexpensive but effective drugs, regular supervisory visits to health facilities, and village campaigns to improve
Contradictory or complementary results?
The results of the Mwanza trial had a major influence on HIV-1 prevention policies in many countries around the world. However, the unexpected results of the Rakai trial have resulted in uncertainty among policy-makers and donor agencies. We believe that the differences in the trial results are not contradictory but complementary, that they can assist rather than confuse policy decisions, that they make a major contribution to our understanding of interactions between STDs and HIV-1, and that
Implications for policy
What can we say based on current evidence about the role of STD control in HIV-1 prevention? First, there is overwhelming evidence that STDs do act as cofactors enhancing the transmission of HIV-1, and that this helps to explain the rapid spread of infection in populations with high STD rates. Mwanza and Rakai data are consistent with previous epidemiological findings. Thus, STD control needs to remain high on the agenda of AIDS control programmes as one of several strategies to reduce HIV-1
Questions for research
Three main areas of research are required for future policy decisions: operational research, clinical and epidemiological research, and impact evaluation of intervention strategies.
Conclusions
TD control remains an urgent public-health priority for the prevention of HIV-1 and the prevention of the complications and sequelae of STDs. Effective STD treatment services remain an essential component of a basic package of health care, to which all people should have access. Improved STD treatment remains the only intervention that has been proven through a randomised trial to be effective in reducing HIV-1 incidence among adults in the general population in Africa. A renewed commitment is
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