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Disentangling Contributions of Reproductive Tract Infections to HIV Acquisition in African Women

van de Wijgert, Janneke H. H. M. PHD, MPH, MSc*††; Morrison, Charles S. PHD, MPH; Brown, Joelle PHD, MPH; Kwok, Cynthia MSPH; Van Der Pol, Barbara PHD, MPH§; Chipato, Tsungai MBChB, FRCOG; Byamugisha, Josaphat K. MBChB, Dip Obs, MMed, PHD; Padian, Nancy PHD#; Salata, Robert A. MD**

Sexually Transmitted Diseases: June 2009 - Volume 36 - Issue 6 - p 357-364
doi: 10.1097/OLQ.0b013e3181a4f695

Objective: To estimate the effects of reproductive tract infections (RTIs) on HIV acquisition among Zimbabwean and Ugandan women.

Methods: A multicenter prospective observational cohort study enrolled 4439 HIV-uninfected women aged 18 to 35 attending family planning clinics in Zimbabwe and Uganda. Participants were interviewed, and tested for HIV and RTIs every 3 months for 15 to 24 months. They received HIV risk reduction counseling, male condoms, and treatment for curable RTIs.

Results: Despite HIV risk reduction counseling and regular screening and treatment for RTIs, the HIV incidence did not decline during the study. Positive HSV-2 serostatus at baseline (hazard ratio [HR] = 3.69, 95% confidence interval = 2.45–5.55), incident HSV-2 (HR = 5.35, 3.06–9.36), incident Neisseria gonorrhoeae (HR = 5.46, 3.41–8.75), and altered vaginal flora during the study (bacterial vaginosis [BV]: HR = 2.12, 1.50–3.01; and intermediate flora: HR = 2.02, 1.39–2.95) were independently associated with HIV acquisition after controlling for demographic and behavioral covariates and other RTIs (Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, and vaginal yeasts). For N. gonorrhoeae, C. trachomatis, T. vaginalis, and vaginal yeasts, the risk of HIV acquisition increased when the infection was identified at the visit before the HIV-detection visit or with the duration of infection. Population attributable risk percent (PAR%) calculations show that HSV-2 contributes most to acquisition of new HIV infections (50.4% for baseline HSV-2 and 7.9% for incident HSV-2), followed by altered vaginal flora (17.2% for bacterial vaginosis and 11.8% for intermediate flora).

Conclusions: A substantial proportion of new HIV infections in Zimbabwean and Ugandan women are attributable to RTIs, particularly HSV-2 and altered vaginal flora.

Secondary analyses of the “Hormonal Contraception and Risk of HIV Acquisition” study showed that a substantial proportion of new HIV infections in Zimbabwean and Ugandan women are still attributable to reproductive tract infections, most importantly herpes simplex virus 2 followed by altered vaginal flora.

*Academic Medical Center, Center for Poverty-related Communicable Diseases (AMC-CPCD), Amsterdam, the Netherlands; †Family Health International (FHI), Research Triangle Park, North Carolina; ‡Department of Epidemiology, University of California at Los Angeles (UCLA), Los Angeles, California; §Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; ∥Department of Obstetrics and Gynecology, University of Zimbabwe Medical School, Harare, Zimbabwe; ¶Department of Obstetrics and Gynecology, Makarere University Medical School, Kampala, Uganda; #Department of Medicine, RTI International, San Francisco, California; **Case Western Reserve University, Cleveland, Ohio; and ††Academic Medical Center, Center for Poverty-related Communicable Diseases (CPCD) and Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam the Netherlands.

The authors thank the study participants and all members of the Hormonal Contraception and the Risk of HIV Acquisition (HC-HIV) study team; Geetha Beauchamp for her contributions to the data analysis; and Ward Cates and Paul Feldblum for reviewing early drafts of this article.

Supported by the US National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services through a contract with Family Health International (contract N01-HD-0-3310).

The content of this publication does not necessarily reflect the views and policies of the US Department of Health and Human Services or FHI, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

None of the authors has a commercial or other association that might pose a conflict of interest.

Correspondence: Janneke van de Wijgert, PhD, MPH, Academic Medical Center, Center for Poverty-related Communicable Diseases, Meibergdreef 9 T0-120, PO Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail:

Received for publication July 31, 2008, and accepted December 1, 2008.

© Copyright 2009 American Sexually Transmitted Diseases Association