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Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe

Brown, Joelle Ma; Wald, Annad; Hubbard, Alanc; Rungruengthanakit, Kittipongg; Chipato, Tsungaih; Rugpao, Sungwalg; Mmiro, Francisf; Celentano, David Di; Salata, Robert Sj; Morrison, Charles Sk; Richardson, Barbra Ae; Padian, Nancy Sb

doi: 10.1097/QAD.0b013e3282004929
Basic Science

Background: An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection among men, but prospective studies in women have yielded mixed results.

Objective: To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries.

Design: Prospective cohort study.

Methods: HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15–24 months among 4531 sexually active, HIV-uninfected women aged 18–35 years from Uganda and Zimbabwe. The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model, adjusted for covariates.

Results: HSV-2 seroprevalence at enrollment was 52% in Uganda and 53% in Zimbabwe; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Uganda and Zimbabwe, respectively. In Uganda, the hazard ratio (HR) for HIV was 2.8 [95% confidence interval (CI), 1.5–5.3] among women with seroprevalent HSV-2 and 4.6 (95% CI, 1.6–13.1) among women with seroincident HSV-2, adjusted for confounding. In Zimbabwe, the HR for HIV was 4.4 (95% CI, 2.7–7.2) among women with seroprevalent HSV-2, and 8.6 (95% CI, 4.3–17.1) among women with seroincident HSV-2, adjusted for confounding. The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42% in Uganda and 65% in Zimbabwe.

Conclusions: HSV-2 plays an important role in the acquisition of HIV among women. Efforts to implement known HSV-2 control measures, as well as identify additional measures to control HSV-2, are urgently needed to curb the spread of HIV.

From the aDepartment of Epidemiology, University of California at Los Angeles, USA

bDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of California at San Francisco, USA

cDepartment of Epidemiology and Biostatistics, University of California at Berkeley, California, USA

dDepartments of Medicine and Epidemiology, University of Washington, USA

eCenter for HIV/AIDS Research & Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, Washington State, USA

fFaculty of Medicine, Makerere University, Kampala, Uganda

gResearch Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand

hDepartment of Obstetrics and Gynaecology, University of Zimbabwe, Harare, Zimbabwe

iDepartment of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

jDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio

kClinical Research Department, Family Health International, Research Triangle Park, North Carolina, USA.

Received 1 February, 2007

Accepted 12 March, 2007

Correspondence and requests for reprints to Dr J.M. Brown, University of California, Los Angeles, 10880 Wilshire Blvd, Suite 540, Los Angeles, CA 90095, USA. E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.