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      Estimating the Cost-Effectiveness of Pre-Exposure Prophylaxis to Reduce HIV-1 and HSV-2 Incidence in HIV-Serodiscordant Couples in South Africa

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          Abstract

          Objective

          To estimate the cost-effectiveness of daily oral tenofovir-based PrEP, with a protective effect against HSV-2 as well as HIV-1, among HIV-1 serodiscordant couples in South Africa.

          Methods

          We incorporated HSV-2 acquisition, transmission, and interaction with HIV-1 into a microsimulation model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1 1infected partner, and for one year thereafter.

          Results

          We estimate the cost per disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP has no effect on reducing HSV-2 acquisition, and one in which there is a 33% reduction. After a twenty-year intervention, the cost per DALY averted is estimated to be $10,383 and $9,757, respectively – a 6% reduction, given the additional benefit of reduced HSV-2 acquisition. If all couples are discordant for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows that the impact is limited by HSV-2 concordance in couples.

          Conclusion

          After a 20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is estimated to be modestly lower than without any effect, providing an increase of health benefits in addition to HIV-1 prevention at no extra cost. The small degree of the effect is in part due to a high prevalence of HSV-2 infection in HIV-1 serodiscordant couples in South Africa.

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          Most cited references 35

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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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            Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes.

            The Zambian Ministry of Health has scaled-up human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka, using predominately nonphysician clinicians. To report on the feasibility and early outcomes of the program. Open cohort evaluation of antiretroviral-naive adults treated at 18 primary care facilities between April 26, 2004, and November 5, 2005. Data were entered in real time into an electronic patient tracking system. Those meeting criteria for antiretroviral therapy (ART) received drugs according to Zambian national guidelines. Survival, regimen failure rates, and CD4 cell response. We enrolled 21,755 adults into HIV care, and 16,198 (75%) started ART. Among those starting ART, 9864 (61%) were women. Of 15,866 patients with documented World Health Organization (WHO) staging, 11,573 (73%) were stage III or IV, and the mean (SD) entry CD4 cell count among the 15,336 patients with a baseline result was 143/microL (123/microL). Of 1142 patients receiving ART who died, 1120 had a reliable date of death. Of these patients, 792 (71%) died within 90 days of starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%) died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In multivariable analysis, mortality was strongly associated with CD4 cell count between 50/microL and 199/microL (adjusted hazard ratio [AHR], 1.4; 95% confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/microL (AHR, 2.2; 95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI, 1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11,714 patients at risk, 861 failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean (SD) CD4 cell count increase was 175/microL (174/microL) in 1361 of 1519 patients (90%) receiving treatment long enough to have a 12-month repeat. Massive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes.
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              Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review.

              Information on age- and sex-specific prevalence of herpes simplex virus (HSV) types 2 and 1 infections is essential to optimize genital herpes control strategies, which increase in importance because accumulating data indicate that HSV-2 infection may increase acquisition and transmission of human immunodeficiency virus. This review summarizes data from peer-reviewed publications of type-specific HSV seroepidemiologic surveys. HSV-2 prevalence is, in general, highest in Africa and the Americas, lower in western and southern Europe than in northern Europe and North America, and lowest in Asia. HSV-2 and -1 prevalence, overall and by age, varies markedly by country, region within country, and population subgroup. Age-specific HSV-2 prevalence is usually higher in women than men and in populations with higher risk sexual behavior. HSV-2 prevalence has increased in the United States but national data from other countries are unavailable. HSV-1 infection is acquired during childhood and adolescence and is markedly more widespread than HSV-2 infection. Further studies are needed in many geographic areas.
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                Author and article information

                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                23 January 2015
                2015
                : 10
                : 1
                Affiliations
                [1 ]Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
                [2 ]Departments of Global Health, Medicine and Epidemiology, University of Washington, Seattle, Washington, United States of America
                [3 ]Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa
                Author notes

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

                Conceived and designed the experiments: BLJ IC MP TBH. Performed the experiments: BLJ. Analyzed the data: BLJ IC MP TBH. Wrote the paper: BLJ IC MP CC JMB SDM TBH.

                Article
                PONE-D-14-31186
                10.1371/journal.pone.0115511
                4304839
                25616135

                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

                Page count
                Figures: 2, Tables: 1, Pages: 11
                Product
                Funding
                B.L.J., I.C., and T.B.H. would like to thank the Bill & Melinda Gates Foundation for funding this research via a sub-contract from Georgetown University. This analysis was also supported by the National Institute of Mental Health of the US National Institutes of Health (R01MH095507) to J.M.B. The content is the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                The data used are from the Partners in Prevention HSV/HIV Transmission Study, and were obtained from a third party. However, the data are available upon request from the principal investigators of this study, Connie Celum ( ccelum@ 123456uw.edu ) and Jared Baeten ( jbaeten@ 123456uw.edu ).

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