Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics: recommendations and key considerations: web annex 2.2. male circumcision and the risk of HIV infection in women: systematic review and meta-analysis

WEB ANNEX 2.2 MALE CIRCUMCISION AND THE RISK OF HIV INFECTION IN WOMEN: SYSTEMATIC REVIEW AND META-ANALYSIS 2.2 PREVENTING HIV THROUGH SAFE VOLUNTARY MEDICAL MALE CIRCUMCISION FOR ADOLESCENT BOYS AND MEN IN GENERALIZED HIV EPIDEMICS Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics: recommendations and key considerations. Web Annex 2.2. Male circumcision and the risk of HIV infection in women: systematic review and meta-analysis ISBN 978-92-4-000928-8 (electronic version) © World Health Organization 2020 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC- SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. 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The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. This publication forms part of the WHO guideline entitled Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics: recommendations and key considerations. It is being made publicly available for transparency purposes and information, in accordance with the WHO handbook for guideline development, 2nd edition (2014). 3Web Annex 2.2: Male circumcision and the risk of HIV infection in women: systematic review and meta-analysis WEB ANNEX 2.2 MALE CIRCUMCISION AND THE RISK OF HIV INFECTION IN WOMEN: SYSTEMATIC REVIEW AND META-ANALYSIS 20th International Conference on AIDS and STIs in Africa, 2019; Kigali, Rwanda FRPEC216 – Male Circumcision and HIV Infection in Women – Systematic Review of Evidence Farley Tim1, Samuelson Julia2, Grabowski M Kate3, Ameyan Wole2, Gray Ronald H4, Kagaayi Joseph5, Baggaley Rachel2 1Sigma3 Services SARL, Nyon, Switzerland, 2World Health Organization, Department of HIV, Geneva, Switzerland, 3Johns Hopkins School of Medicine, Department of Pathology, Baltimore, United States, 4Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, United States, 5Rakai Health Sciences Program, Entebbe, Uganda Background: Women benefit indirectly from male circumcision because of reduced HIV acquisition and hence prevalence in men. Observational studies suggested HIV-negative women with HIV+ circumcised partner were less likely to acquire HIV than those with uncircumcised partner, but a randomized trial (RCT) of circumcision in HIV+ men suggested higher though not statistically significant risk of female HIV acquisition. To inform new WHO guidance on Voluntary Medical Male Circumcision (VMMC) for HIV prevention, we conducted a systematic review of impact of circumcision on HIV infection in women. Methods: PubMed search for ‘HIV infection’ and ‘male circumcision´ identified 1 RCT and 6 observational cohort studies with data on HIV risk in women according to partner’s circumcision status. Results: HIV+ men in an RCT of immediate or delayed circumcision enrolled female partners to assess impact on women. HIV incidence was 11.5/100 py in partners of circumcised and 6.9/100 py of uncircumcised men (incidence ratio [IR] 1.6 [95% CI 0.6–3.7]). Excess risk was confined to couples who resumed sex before wound healing, consistent with a study of HIV+ men showing higher penile HIV shedding for 3 weeks following circumcision (Tobian PLoS Med 2015). Two observational cohorts in serodiscordant couples showed lower incidence in partners of circumcised than uncircumcised HIV+ men (pooled adjusted IR 0.59 [0.35–0.99]). In 4 cohorts of women with undocumented or mixed partner HIV status pooled adjusted IR was 0.75 (0.56–1.00). See Fig. 1. Conclusions: The discrepancy between the RCT and observational cohorts is likely explained by duration of exposure to the circumcised partner (several years in the observational studies, only recently in the RCT) and resumption of intercourse before wound healing. We believe there is biological plausibility for partners of circumcised men to be at lower long-term risk of HIV – less viral shedding after wound healing (Tobian PLoS Med 2015), fewer penile anaerobes following circumcision (Liu MBio 2013), lower incidence of bacterial vaginosis (BV) and severe BV in partners of circumcised men (Gray AJOG 2009) – but time until lower risk manifests is unknown. The short-term post-circumcision risk underlines the importance of HIV testing before VMMC, delaying VMMC for HIV+ men until stable on ART for their own health and preventing onward transmission, stressing sexual abstinence until wound healing, and the value of reaching adolescents prior to sexual debut. Source: www.professionalabstracts.com/icasa2019/iplanner/#/presentation/2986 4 Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics Fig. 1. 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The effects of male circumcision on female partners’ genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda. AJOG. 2009; 200(42): e1-e7. Gray RH, Kiwanuka N, Quinn TC, Sewankambo NK, Serwadda D, Mangen FW, et al. Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. AIDS. 2000; 14: 2371-81. Kapiga SH, Lyamuya EF, Lwihula GK, Hunter DJ. The incidence of HIV infection among women using family planning methods in Dar es Salaam, Tanzania. AIDS. 1998; 12(1): 75-84. Liu CM, Hungate BA, Tobian AAR, Serwadda D, Ravel J, Lester R, et al. Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria. Mbio. 2013; 4(2): e00076-13. Tobian AAR, Kigozi G, Manucci J, Grabowski MK, Serwadda D, Musoke R, et al. HIV shedding from male circumcision wounds in HIV- Infected men: A prospective cohort study. PLoS Med. 2015; 12(4): e1001820. Turner AN, Morrison CS, Padian NS, Kaufman JS, Salata RA, Chipato T, et al. 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