What Is the Burden of Heterosexually Acquired HIV Due to HSV-2? Global and Regional Model-Based Estimates of the Proportion and Number of HIV Infections Attributable to HSV-2 Infection.

Background: Biological and epidemiological evidence suggest that herpes simplex virus type 2 (HSV-2) elevates HIV acquisition and transmission risks. We improved previous estimates of the contribution of HSV-2 to HIV infections by using a dynamic transmission model.
Setting: World Health Organization regions.
Methods: We developed a mathematical model of HSV-2/HIV transmission among 15- to 49-year-old heterosexual, non-drug-injecting populations, calibrated using region-specific demographic and HSV-2/HIV epidemiological data. We derived global and regional estimates of the contribution of HSV-2 to HIV infection over 10 years [the transmission population-attributable fraction (tPAF)] under 3 additive scenarios, assuming: (1) HSV-2 increases only HIV acquisition risk (conservative); (2) HSV-2 also increases HIV transmission risk (liberal); and (3) HIV or antiretroviral therapy (ART) also modifies HSV-2 transmission risk, and HSV-2 decreases ART effect on HIV transmission risk (fully liberal).
Results: Under the conservative scenario, the predicted tPAF was 37.3% (95% uncertainty interval: 33.4%-43.2%), and an estimated 5.6 (4.5-7.0) million incident heterosexual HIV infections were due to HSV-2 globally over 2009-2018. The contribution of HSV-2 to HIV infections was largest for the African region [tPAF = 42.6% (38.0%-51.2%)] and lowest for the European region [tPAF = 11.2% (7.9%-13.8%)]. The tPAF was higher among female sex workers, their clients, and older populations, reflecting their higher HSV-2 prevalence. The tPAF was approximately 50% and 1.3- to 2.4-fold higher for the liberal or fully liberal scenario than the conservative scenario across regions.
Conclusion: HSV-2 may have contributed to at least 37% of incident HIV infections in the past decade worldwide, and even more in Africa, and may continue to do so despite increased ART access unless future improved HSV-2 control measures, such as vaccines, become available.
Competing Interests: K.J.L. and K.M.E.T. report a grant from GSK outside the submitted work. This work was funded by the World Health Organization, through the UNDP-UNFPAUNICEF-WHO-World Bank Special Program of Research, Development, and Research Training in Human Reproduction, a cosponsored program executed by the WHO, and through support from the US National Institute of Allergy and Infectious Diseases, part of the US National Institutes of Health (NIH) (NIH U01 AI108543). This work was partly supported by the HPTN Modelling Centre, which is funded by the NIH (NIH UM1 AI068617) through the HPTN Statistical and Data Management Center. R.S., H.L.C., R.F.B., J.S., L.S., and M.C.B. acknowledged funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth, and Development Office (FCDO), under the MRC/FCDO Concordat agreement and are also part of the EDCTP2 program supported by the European Union. S.G. acknowledged additional funding support from NIH (U01AI139547). K.J.L. and K.M.E.T. thank the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Evaluation of Interventions at the University of Bristol, in partnership with Public Health England (PHE), for research support. RH received funding from the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, which is also part of the EDCTP2 program supported by the European Union. Grant Ref: MR/R010161/1. R.F.B. is supported by a Wellcome Trust Institutional Strategic Support Fund Fellowship (204801/Z/16/Z). P.V. also acknowledged support from the NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol. The authors alone are responsible for the views expressed in this article, and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated, the WHO, the NHS, the NIHR the Department of Health and Social Care, or Public Health England. The remaining authors have no conflicts of interest to disclose.
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