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      Prevalence, Incidence and Determinants of Herpes Simplex Virus Type 2 Infection among HIV-Seronegative Women at High-Risk of HIV Infection: A Prospective Study in Beira, Mozambique

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          To estimate the prevalence, incidence and determinants of herpes simplex type 2 (HSV-2) infection, and associations between HSV-2 and incident HIV infection, among women at higher risk for HIV infection in Beira, Mozambique.


          Between 2009 and 2012, 411 women aged 18–35 years at higher risk of HIV acquisition (defined as having had two or more sexual partners in the month prior to study enrollment) were enrolled and followed monthly for one year. At each study visit, they were counseled, interviewed, and tested for HSV-2 and HIV antibodies.


          The HSV-2 prevalence at baseline was 60.6% (95% CI: 55.7% –65.4%). Increasing age (aOR = 2.94, 95% CI: 1.74–4.97, P<0.001 and aOR = 3.39, 95% CI: 1.58–7.29, P = 0.002 for age groups of 21–24 and 25–35 years old respectively), lower educational level (aOR = 1.81, 95% CI: 1.09–3.02, P = 0.022), working full time (aOR = 8.56, 95% CI: 1.01–72.53, P = 0.049) and having practiced oral sex (aOR = 3.02, 95% CI: 1.16–7.89, P = 0.024) were strongly associated with prevalent HSV-2 infection. Thirty one participants seroconverted for HSV-2 (20.5%; 95% CI: 14.4% –27.9%) and 22 for HIV during the study period. The frequency of vaginal sex with a casual partner using a condom in the last 7 days was independently associated with incident HSV-2 infection (aOR = 1.91, 95% CI: 1.05–3.47, P = 0.034). Positive HSV-2 serology at baseline was not significantly associated with risk of subsequent HIV seroconversion.


          Young women engaging in risky sexual behaviors in Beira had high prevalence and incidence of HSV-2 infection. Improved primary HSV-2 control strategies are urgently needed in Beira.

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          Most cited references 27

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          Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

          To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. Systematic review and meta-analysis of longitudinal studies. PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.
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            Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis.

             Anna Wald,  K. Link (2002)
            To determine the contribution of herpes simplex type 2 (HSV-2) infection to the risk of human immunodeficiency virus (HIV) acquisition, a systematic review of literature and data synthesis were done. Thirty-one studies addressed the risk of HIV infection in HSV-2-seropositive persons. For 9 cohort and nested case-control studies that documented HSV-2 infection before HIV acquisition, the risk estimate was 2.1 (95% confidence interval, 1.4-3.2). Thus, the attributable risk percentage of HIV to HSV-2 was 52%, and the population attributable risk percentage was 19% in populations with 22% HSV-2 prevalence but increased to 47% in populations with 80% HSV-2 prevalence. For 22 case-control and cross-sectional studies, the risk estimate was 3.9 (95% confidence interval, 3.1-5.1), but the temporal sequence of the 2 infections cannot be documented. Control strategies for HSV-2 need to be incorporated into control of sexually transmitted infections as a strategy for HIV prevention.
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              The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.

              To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

                Author and article information

                [1 ]Universidade Católica de Moçambique/Catholic University of Mozambique (UCM), Centro de Investigação de Doenças Infecciosas/Center for Infectious Disease Research (CIDI), Beira, Mozambique
                [2 ]FHI 360, Clinical Sciences Unit, Durham, North Carolina, United States of America
                [3 ]United States Military HIV Research Program (MHRP), Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF), Bethesda, Maryland, United States of America
                [4 ]University of Queensland, Infectious Disease Epidemiology Unit, School of Population Health, Brisbane, Australia
                [5 ]Amsterdam Institute for Global Health and Development (AIGHD) and Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
                [6 ]University of Liverpool, Institute of Infection and Global Health, Liverpool, United Kingdom
                Geisel School of Medicine at Dartmouth, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PJF JHvW. Performed the experiments: IM KD PJF AZ FC JJF JHvW. Analyzed the data: IM ACAC PLC JHvW. Contributed reagents/materials/analysis tools: IM KD PJF PLC JHvW. Wrote the paper: IM KD PJF ACAC JHvW AZ FC JJF PLC.

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                24 February 2014
                : 9
                : 2

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Pages: 10
                This study was partly funded by the U.S. Agency for International Development (USAID), under Cooperative Agreement No. GPO-A-00-05-00022-00, the Contraceptive and Reproductive Health Technologies Research and Utilization (CRTU) Program, and Cooperative Agreement No. GHO-A-00-09-00016-00, the Preventive Technologies Agreement (PTA). The study also received funding from the European and Developing Countries Clinical Trials Partnership (EDCTP) through the AfrEVacc project. IM was partially supported by the Australian Government (AUSAID) through Australian Development Scholarship (ADS) program. ACAC is funded by a NHMRC Career Development Award (#631619). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and should not be construed to represent the positions of the funders. The views expressed in this paper are those of the authors and should not be construed to represent the positions of EDCTP, USAID, the U.S. Army or the U.S. Department of Defense.
                Research Article
                Population biology
                Infectious disease epidemiology
                Clinical research design
                Infectious disease epidemiology
                Infectious diseases
                Sexually transmitted diseases
                Herpes simplex
                Viral diseases
                HIV epidemiology
                HIV prevention
                Herpes simplex
                Infectious disease control
                Public health



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