Bulletin of the World Health Organization, 2001, 79:48-58
Voir page 56 le resume en francais. En la pagina 56 figura un resumen en espanol.
In many ways, the public health response to AIDS has been more "scientific" than the responses to other diseases. The epidemic has coincided with moves towards practising evidence-based medicine and the now dominant use of randomized controlled trials in medical research. Thus, it would have been surprising if randomized trials of treatment for sexually transmitted diseases (STDs) had not been performed in the search for a better understanding of HIV transmission. There were specific reasons (1-3) why the two trial trials exploring the relation between STDs and HIV infection in Mwanza in the United Republic of Tanzania, and Rakai in the Republic of Uganda, were conducted (4, 5). However, there was no expectation that the results would diverge. An additional, similar trial will soon be completed in Masaka, Uganda, but this was planned long before publication of the divergent findings.
In Mwanza, the trial of STD treatment produced a 38% reduction in the incidence of HIV-1 infection despite there being only a modest effect on infection with STDs; in Rakai a trial of mass treatment of STDs produced no effect on the incidence of HIV-1 infection but there was a more marked, but still modest, effect on the incidence of STDs compared to Mwanza (3). Although more trials are planned or in progress, this paper argues that the Mwanza and Rakai trials provide enough information to revise the paradigm of the interaction between STDs and HIV. Because basic science and observational studies have already been comprehensively reviewed (3), this analysis focuses on the trials and discusses scientific method, the prevention of HIV transmission, and syndromic management.
Mwanza, Rakai and Masaka: three trials in East Africa
Between late 1989 and mid-1993 three randomized trials were designed to look at the interaction between STDs and HIV at the population level (2). The Mwanza trial began in 1992 and the other two -- taking place less than 300 km away (Fig. 1) -- started before the results of the Mwanza trial had been published.
[Figure 1 ILLUSTRATION OMITTED]
The trial of improved syndromic management of STDs in Mwanza was designed to discover whether, at a population level, individuals infected with STDs are more likely to become infected with, or transmit, HIV (1) and to answer the practical question of how to improve the management of STDs in developing countries (2). The trial in Rakai was also a biomedical trial -- that is, there were no new behavioural interventions. The authors did not try to improve the management of STDs but instead sought to determine whether providing mass treatment in communities where there was a high incidence of HIV transmission, such as roadside settlements, has a beneficial effect on rates of infection with STDs and the incidence of HIV infection. The third trial, in Masaka, compares the effect of health education alone with a "Mwanza plus" package (syndromic management of STDs plus health education) (2).
The hypothesis of the Mwanza trial was that inflammation associated with a symptomatic STD increased both infectiousness (person with STD and HIV positive but partner HIV negative) and susceptibility (,person with STD and HIV negative but partner HIV positive). There was an impressive body of mostly epidemiological evidence at the time the Mwanza trial was designed (1). Recently, substantial basic science data have also accumulated (3). However, the hypothesis underlying the Rakai trial -- that asymptomatic carriage of a bacterial STD has a similar effect on HIV transmission -- is based on very limited evidence, at least in men. In women, data on the association between an asymptomatic STD and infectiousness is mostly qualitative (6, 7); additionally, data on viral load in genital secretions (8) are not as clear as data on men with a symptomatic STD (9). …