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Empirical Observations Underestimate the Proportion of Human Immunodeficiency Virus Infections Attributable to Sexually Transmitted Diseases in the Mwanza and Rakai Sexually Transmitted Disease Treatment Trials: Simulation Results

Orroth, Kate K. PhD*; White, Richard G. MSc*; Korenromp, Eline L. PhD; Bakker, Roel PhD; Changalucha, John MSc; Habbema, J Dik F. PhD; Hayes, Richard J. DSc*

doi: 10.1097/01.olq.0000204667.11192.71

Background and Objectives: Population attributable fractions (PAF) from observational studies may under- or overestimate the contribution of cofactor sexually transmitted disease (STD) to human immunodeficiency virus (HIV) spread. Empirical PAF estimates from the Mwanza and Rakai trials indicated the proportion of HIV infections attributable to STDs was higher in Mwanza than Rakai.

Goal of This Study: Estimate the “true” proportion (PAFM) of HIV infections attributable to STDs in the Mwanza and Rakai STD trial populations and explore how the evaluated interventions prevented HIV infections.

Study Design: The STDSIM model was used to simulate the 2 populations at the baseline of the trials (with no STD treatment interventions) and counterfactual scenarios in which STD cofactor effects on HIV spread were removed either at the start of the trials or 2, 10, and 20 years into the HIV epidemics. Similar methods were used to quantify the contribution of the cure of each STD to overall HIV impact in each site.

Results: In Mwanza, the highest PAFM for the effect of any single STD over the 2 years of the trial was due to chancroid (40%). The PAFM for all curable STD was 65%. In Rakai, herpes simplex virus type 2 (HSV-2) was the most important STD (PAFM = 23%); the PAFM for curable STD was 20%. In both sites, the proportion of new infections due to treatable STD decreased over time. The decrease was greater for Rakai, where a behavioral risk reduction that preceded the trial reduced STD prevalence. In both sites, the importance of HSV-2 increased later in the HIV epidemics and STD increased transmission of HIV more than acquisition of HIV. In the Mwanza trial, treatment of chancroid contributed most to preventing new HIV infections.

Conclusions: PAFs calculated from empirical data underestimated the contribution of STD to HIV spread in the Mwanza and Rakai trial populations because STD effects on HIV transmission (as opposed to acquisition) were not captured in the observationally based studies.

Simulations of the Mwanza and Rakai sexually transmitted disease (STD) treatment trial populations suggest that the proportions of incident HIV infections attributable to curable STD were higher than empirical estimates from the trials.

From the *London School of Hygiene and Tropical Medicine, London, UK; †Department of Public Health, Erasmus University Rotterdam, Rotterdam, the Netherlands; and the ‡National Institute for Medical Research, Mwanza, Tanzania

The authors thank Ron Gray, Maria Wawer, and David Serwadda, as well as the referees, for useful comments on the manuscript. The authors thank the directors of the National Institute for Medical Research and African Medical and Research Foundation, Tanzania, and the Uganda Virus Research Institute for permission to carry out this study and to publish the results. We are grateful to the scientific teams who carried out the intervention trials in Mwanza and Rakai and to the study participants who took part. This work was supported financially by the UK Department for International Development.

Correspondence: Kate K. Orroth, PhD, Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. E-mail:

© Copyright 2006 American Sexually Transmitted Diseases Association