Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics: recommendations and key considerations: web annex 2.1. GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men

WEB ANNEX 2.1 GRADE AND EVIDENCE-TO-DECISION TABLES ON VOLUNTARY MEDICAL MALE CIRCUMCISION FOR HIV PREVENTION AMONG ADOLESCENTS AND MEN 2.1 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 2.1. GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men ISBN 978-92-4-000927-1 (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). 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However, the published material is being distributed without warranty of any kind, either expressed or implied. 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 2.1: GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men WEB ANNEX 2.1 GRADE AND EVIDENCE-TO-DECISION TABLES ON VOLUNTARY MEDICAL MALE CIRCUMCISION FOR HIV PREVENTION AMONG ADOLESCENTS AND MEN Contents Table A2.1.1. GRADE evidence profile: PICO question. Does male circumcision reduce the risk of infection in men exposed to HIV through heterosexual intercourse? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Table A2.1.2. GRADE evidence profile: PICO question. Does male circumcision reduce the risk of infection in women exposed to HIV through heterosexual intercourse? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Fig. A2.1.1. Impact of voluntary medical male circumcision on HIV incidence in heterosexual men . . . . . . . . . . . . . . . . . . . . . . . 6 Fig. A2.1.2. Rates of severe and moderate adverse events in studies of voluntary medical male circumcision for adolescents and men . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Table A2.1.3. GRADE evidence profile: PICO question. Among adolescents under 15 years, compared with older adolescent boys or men, is surgical male circumcision safe? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Table A2.1.4. Evidence-to-decision-making: male circumcision for HIV prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Table A2.1.5. Evidence-to-decision-making: offer of VMMC to younger adolescent boys (ages 10–14 years) . . . . . . . . . . . . . . . . 14 4 Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics Ta bl e A2 .1 .1 . G RA DE e vi de nc e pr ofi le : P IC O qu es tio n. D oe s m al e ci rc um ci si on re du ce th e ris k of in fe ct io n in m en e xp os ed to H IV th ro ug h he te ro se xu al in te rc ou rs e? A ut ho r( s) : T im F ar le y D at e: 2 01 9 Q ue st io n: D oe s m al e ci rc um ci si on re du ce th e ris k of in fe ct io n in m en e xp os ed to H IV th ro ug h he te ro se xu al in te rc ou rs e? Se tt in gs : H ig h H IV in ci de nc e se tt in gs Q ua lit y as se ss m en t N o. o f pa ti en ts a Ef fe ct Q ua lit y Im po rt an ce N o. o f st ud ie s D es ig n Ri sk o f b ia s In co ns is te nc y In di re ct ne ss Im pr ec is io n O th er co ns id er at io ns Ci rc um ci si on Co nt ro l Re la ti ve (9 5% C I) b A bs ol ut e (9 5% C I) c O ut co m e: e ffi ca cy (i nc id en t H IV in fe ct io n) 3 1- 3 ra nd om iz ed co nt ro lle d tr ia ls (R CT ) so m e ris k of bi as d no s er io us in co ns is te nc y no s er io us in di re ct ne ss no im pr ec is io n so m e co nc er ns e 64 /7 79 1 p- y (0 .8 2 pe r 1 00 p -y ) 14 1/ 79 45 (1 .7 7 pe r 1 00 p -y ) IR R 0. 41 (0 .3 0 to 0 .5 6) 10 fe w er p er 10 00 p -y (fr om 8 to 1 2 fe w er ) HI G H CR IT IC AL 2 4, 5 po st -R CT fo llo w - up s tu di es so m e ris k of b ia s f no s er io us in co ns is te nc y no s er io us in di re ct ne ss no im pr ec is io n no ne 95 /1 5 37 2 p- y (0 .6 2 pe r 1 00 p -y ) 10 0/ 51 94 p -y (1 .9 3 pe r 1 00 p -y ) aI RR 0 .3 4 (0 .2 4 to 0 .4 9) 13 fe w er p er 10 00 p -y (fr om 1 0 to 1 5 fe w er ) HI G H CR IT IC AL 5 6- 10 co ho rt s tu di es of m en a t h ig h HI V ris k so m e ris k of bi as g so m e in co ns is te nc y h no s er io us in di re ct ne ss no im pr ec is io n no ne 60 /3 44 4 p- y (1 .7 p er 1 00 p -y ) 25 8/ 47 56 p -y (5 .4 p er 1 00 p -y ) aI RR 0 .2 9 (0 .1 9 to 0 .4 3) 39 fe w er p er 10 00 p -y (fr om 3 1 to 4 4 fe w er ) HI G H CR IT IC AL 4 7, 11 -1 3 po pu la tio n- ba se d co ho rt st ud ie s be fo re ci rc um ci si on sc al e- up so m e ris k of b ia s i no s er io us in co ns is te nc y no s er io us in di re ct ne ss no im pr ec is io n so m e co nc er ns j 58 /9 46 6 k p -y (0 .6 1 pe r 1 00 p -y ) 17 1/ 99 30 k p- y (1 .7 2 pe r 1 00 p -y ) aI RR 0 .4 8 (0 .3 3 to 0 .7 0) 9 fe w er p er 10 00 p -y (fr om 5 to 1 2 fe w er ) HI G H CR IT IC AL 6 14 -1 9 po pu la tio n- ba se d co ho rt st ud ie s du rin g ci rc um ci si on sc al e- up so m e ris k of b ia s l no s er io us in co ns is te nc y no s er io us in di re ct ne ss no im pr ec is io n no ne 21 6/ 28 2 33 m p -y (0 .7 7 pe r 1 00 p -y ) 95 3/ 61 5 53 m p -y (1 .5 5 pe r 1 00 p -y ) aI RR 0 .5 6 (0 .4 9 to 0 .6 4) 7 fe w er p er 10 00 p -y (fr om 6 to 8 fe w er ) HI G H CR IT IC AL 5Web Annex 2.1: GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men Q ua lit y as se ss m en t N o. o f pa ti en ts a Ef fe ct Q ua lit y Im po rt an ce N o. o f st ud ie s D es ig n Ri sk o f b ia s In co ns is te nc y In di re ct ne ss Im pr ec is io n O th er co ns id er at io ns Ci rc um ci si on Co nt ro l Re la ti ve (9 5% C I) b A bs ol ut e (9 5% C I) c O ut co m e: e ffi ca cy (p re va le nt H IV in fe ct io n in c om m un it ie s w it h re ce nt c ir cu m ci si on s ca le u p) 2 16 ,1 9 co m m un ity -b as ed st ud ie s so m e ris k of bi as n so m e in co ns is te nc y o no s er io us in di re ct ne ss no im pr ec is io n no ne 14 85 /7 30 6 (2 03 p er 1 00 0) 24 87 /6 91 0 (3 60 p er 1 00 0) aP R 0. 65 (0 .6 0 to 0 .7 0) 14 8 fe w er p er 10 00 (fr om 1 34 to 1 62 fe w er ) M O DE RA TE IM PO RT AN T N ot es a N um be r o f H IV in fe ct io ns /p er so n- ye ar s ex po su re (p -y ). b Po ol ed in ci de nc e ra te ra tio (I RR ) f ro m s tu dy -s pe ci fic IR Rs (a dj us te d IR R [a IR R] fo r o bs er va tio na l s tu di es ) o r p oo le d ad ju st ed p re va le nc e ra tio (a PR ) w ith w ei gh ts in ve rs el y pr op or tio na l t o va ria nc e. c Es tim at ed fr om p oo le d IR R or a IR R an d in ci de nc e in c on tr ol a rm o r a m on g un ci rc um ci se d m en p oo le d ov er a ll st ud ie s in s ub gr ou p. d Po te nt ia l b ia s du e to im po ss ib ili ty o f b lin di ng p ar tic ip an ts to in te rv en tio n or c on tr ol . e Al l t hr ee R CT s st op pe d ea rly d ue to s tr on g pr ot ec tiv e ef fe ct . E ffe ct s iz e m ay b e ex ag ge ra te d. f Po te nt ia l b ia s du e to s el f-s el ec tio n to c irc um ci si on fo llo w in g cl os ur e of R CT s an d di ss em in at io n of s tu dy re su lts . A dj us tm en t f or li ke ly c on fo un de rs h ad li tt le im pa ct o n ris k es tim at es , b ut re si du al c on fo un di ng c an no t b e ex cl ud ed . g Po te nt ia l b ia s du e to u nm ea su re d co nf ou nd in g, s el f-r ep or te d ci rc um ci si on s ta tu s (o ne s tu dy ). h So m e he te ro ge ne ity in m ag ni tu de o f e ffe ct , r efl ec tin g di ve rs ity o f h ig h- ris k po pu la tio ns . i Po te nt ia l b ia s du e to u nm ea su re d co nf ou nd in g, s el f-r ep or te d ci rc um ci si on s ta tu s, in ad eq ua te a dj us tm en t f or p ot en tia l c on fo un di ng fa ct or s (o ne s tu dy ), lo ng in te rv al b et w ee n ba se lin e an d fo llo w -u p su rv ey s (o ne s tu dy ). j HI V in ci de nc e es tim at ed fr om c ro ss -s ec tio na l a ss ay ra th er th an re pe at s er ol og y (o ne s tu dy ). k N um be r o f H IV in fe ct io ns a nd p er so n- ye ar s fro m th re e Af ric an s tu di es o nl y. l Po te nt ia l b ia s du e to u nm ea su re d co nf ou nd in g, s el f-r ep or te d ci rc um ci si on s ta tu s (fo ur s tu di es ), fa ilu re to a cc ou nt fo r m en c irc um ci se d du rin g fo llo w -u p pe rio d an d in ad eq ua te a dj us tm en t f or p ot en tia l c on fo un de rs (o ne s tu dy ). m E xc lu di ng o ne s tu dy fo r w hi ch n o in fo rm at io n av ai la bl e. 16 n Po te nt ia l b ia s du e to u nm ea su re d co nf ou nd in g, s el f-r ep or te d ci rc um ci si on s ta tu s (o ne s tu dy ). o So m e he te ro ge ne ity in m ag ni tu de o f e ffe ct . Ta bl e A2 .1 .1 . ( co nt in ue d) 6 Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics Ta bl e A2 .1 .2 . G RA DE e vi de nc e pr ofi le : P IC O qu es tio n. D oe s m al e ci rc um ci si on re du ce th e ris k of in fe ct io n in w om en e xp os ed to H IV th ro ug h he te ro se xu al in te rc ou rs e? A ut ho r( s) : T im F ar le y D at e: 2 01 9 Q ue st io n: D oe s m al e ci rc um ci si on re du ce th e ris k of in fe ct io n in w om en e xp os ed to H IV th ro ug h he te ro se xu al in te rc ou rs e? Se tt in gs : H ig h H IV in ci de nc e se tt in gs Q ua lit y as se ss m en t N o. o f pa ti en ts a Ef fe ct Q ua lit y Im po rt an ce N o. o f st ud ie s D es ig n Ri sk o f b ia s In co ns is te nc y In di re ct ne ss Im pr ec is io n O th er co ns id er at io ns Ci rc um ci si on Co nt ro l Re la ti ve (9 5% C I) b A bs ol ut e (9 5% CI ) c O ut co m e: ri sk o f H IV in fe ct io n in w om en (s ec on da ry , i nd ire ct b en efi t t o w om en ) 1 20 ra nd om iz ed co nt ro lle d tr ia l i n HI V- in fe ct ed m en se rio us ri sk o f bi as d no s er io us in co ns is te nc y no s er io us in di re ct ne ss se rio us im pr ec is io n e no ne 17 /1 48 p -y (1 1. 5 pe r 1 00 p -y ) 8/ 11 5 p- y (6 .9 p er 1 00 p -y ) IR R 1. 49 (0 .6 2 to 3 .5 7) 34 m or e pe r 10 00 p -y (fr om 2 6 fe w er to 17 8 m or e) VE RY L O W CR IT IC AL 2 7, 21 co ho rt s tu di es o f se ro di sc or da nt co up le s so m e ris k of b ia s f no s er io us in co ns is te nc y no s er io us in di re ct ne ss so m e im pr ec is io n e no ne 19 /6 46 p -y (2 .9 4 pe r 1 00 p -y ) 94 /1 44 5 p- y (6 .5 1 pe r 1 00 p -y ) IR R 0. 59 (0 .3 5 to 0 .9 9) 27 fe w er p er 10 00 p -y (fr om 0 to 2 7 fe w er ) LO W CR IT IC AL 4 18 ,2 2- 24 co ho rt s tu di es of w om en w ith p ar tn er s’ HI V st at us un do cu m en te d or m ix ed m od er at e ris k of bi as g no in co ns is te nc y no in di re ct ne ss so m e im pr ec is io n e no ne 97 /7 41 2 p- y (1 .3 1 pe r 1 00 p -y ) 31 1/ 21 6 78 p -y (1 .4 3 pe r 1 00 p -y ) IR R 0. 75 (0 .5 6 to 1 .0 0) 4 fe w er p er 10 00 p -y (fr om 0 to 6 fe w er ) LO W CR IT IC AL N ot es a N um be r o f H IV in fe ct io ns /p er so n- ye ar s ex po su re (p -y ). b Po ol ed in ci de nc e ra te ra tio (I RR ) f ro m s tu dy -s pe ci fic IR Rs w ith w ei gh ts in ve rs el y pr op or tio na l t o va ria nc e. c Es tim at ed fr om p oo le d IR R an d in ci de nc e in c on tr ol a rm o r a m on g un ci rc um ci se d m en p oo le d ov er a ll st ud ie s in s ub gr ou p. d Se rio us ri sk o f b ia s du e to H IV -in fe ct ed m en ra nd om iz ed to c irc um ci si on o r c on tr ol a rm s bu t o ut co m e as se ss ed in s ub se t w ith d oc um en te d HI V- ne ga tiv e co ns en tin g fe m al e pa rt ne rs (1 7% o f o rig in al ly ra nd om iz ed c oh or t). S om e ris k of b ia s du e to im po ss ib ili ty o f b lin di ng p ar tic ip an ts to g ro up a llo ca tio n. e Sm al l n um be r o f i nc id en t H IV in fe ct io ns a nd w id e co nfi de nc e in te rv al s. f Po te nt ia l b ia s du e to u nm ea su re d co nf ou nd in g, s el f-r ep or te d ci rc um ci si on s ta tu s (o ne s tu dy ). g Po te nt ia l b ia s du e to u nm ea su re d co nf ou nd in g, p ar tn er ’s ci rc um ci si on s ta tu s re po rt ed b y w om an , f ai lu re to a cc ou nt fo r c ha ng es in c irc um ci si on s ta tu s du rin g fo llo w -u p (tw o st ud ie s) . 7Web Annex 2.1: GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men A) Randomised controlled trials Auvert 2005 Bailey 2007 Gray 2007 I-V Subtotal (I-squared = 0.0%, p = 0.983) D+L Subtotal B) Extended follow-up of former RCT participants Mehta 2013 Gray 2012 I-V Subtotal (I-squared = 35.4%, p = 0.213) D+L Subtotal C) Cohorts of men at high risk of HIV infection Cameron 1989 Lavreys 1999 Gray 2000 Reynolds 2004 Hughes 2012 I-V Subtotal (I-squared = 67.0%, p = 0.017) D+L Subtotal D) Community-based cohorts before circumcision scale-up Gray 2000 Shaffer 2007 Kim 2016 Dandona 2013 I-V Subtotal (I-squared = 33.9%, p = 0.209) D+L Subtotal E) Community-based cohorts during circumcision scale-up Grabowski 2017 Lissouba 2011 Auvert 2013 Vandormael 2019 Borgdorff 2018 Kagaayi 2019 I-V Subtotal (I-squared = 0.0%, p = 0.500) D+L Subtotal Year Author ZAF KEN UGA KEN UGA KEN KEN UGA IND S&E Afr UGA KEN KEN IND UGA ZAF ZAF ZAF KEN UGA Country 2002-2004 2002-2006 2002-2006 2002-2010 2006-2010 1986-1987 1993-1997 1994-1998 1993-2001 2004-2008 1994-1998 2003-2006 2007-2007 2004-2011 1999-2016 2007-2008 2010-2011 2005-2017 2010-2016 2011-2017 period Study 0.40 (0.24, 0.67) 0.41 (0.24, 0.70) 0.43 (0.24, 0.76) 0.41 (0.30, 0.56) 0.41 (0.30, 0.56) 0.42 (0.26, 0.67) 0.27 (0.16, 0.45) 0.34 (0.24, 0.49) 0.34 (0.22, 0.53) 0.12 (0.04, 0.34) 0.25 (0.12, 0.53) 0.00 (0.00, 0.22) 0.15 (0.04, 0.59) 0.53 (0.29, 0.96) 0.29 (0.19, 0.43) 0.21 (0.09, 0.47) 0.53 (0.33, 0.86) 0.34 (0.16, 0.73) 0.88 (0.30, 2.53) 0.07 (0.01, 0.82) 0.48 (0.33, 0.70) 0.47 (0.27, 0.80) 0.62 (0.48, 0.80) 0.35 (0.14, 0.88) 0.41 (0.24, 0.72) 0.58 (0.47, 0.71) 0.66 (0.38, 1.14) 0.46 (0.32, 0.67) 0.56 (0.49, 0.64) 0.56 (0.49, 0.64) ES (95% CI) 35.95 34.03 30.03 100.00 55.20 44.80 100.00 15.64 29.42 1.01 8.64 45.29 100.00 60.34 24.61 12.63 2.41 100.00 29.50 2.14 5.91 43.03 6.02 13.41 100.00 (I-V) Weight % 1.00.1 0.2 0.3 0.5 0.7 Incidence ratio (95% CI) Fig. A2.1.1. Impact of voluntary medical male circumcision on HIV incidence in heterosexual men BWA = Botswana, IND = India, KEN = Kenya, UGA = Uganda, ZAF = South Africa, S&E Afr = seven countries in East and Southern Africa (BWA, KEN, RWA = Rwanda, TZA = United Republic of Tanzania, UGA, ZAF, ZMB = Zambia) Source: Farley TMM, Samuelson J, Grabowski MK, Ameyan W, Gray RH, Baggaley R. Impact of male circumcision on risk of HIV infection in men in a changing epidemic context – systematic review and meta-analysis. J Int AIDS Soc. 2020;23(6):e25490. References for Tables A2.1.1 and A2.1.2 and Fig. A2.1.1 1. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med. 2005; 2(11): e298. 2. Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007; 369(9562): 643-56. 3. Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007; 369(9562): 657-66. 4. Mehta SD, Moses S, Agot K, Odoyo-June E, Li H, Maclean I, et al. The long-term efficacy of medical male circumcision against HIV acquisition. AIDS. 2013; 27(18): 2899-907. 5. Gray R, Kigozi G, Kong X, Ssempiija V, Makumbi F, Wattya S, et al. The effectiveness of male circumcision for HIV prevention and effects on risk behaviors in a posttrial follow-up study. AIDS. 2012; 26(5): 609-15. 6. Cameron DW, Simonsen JN, D’Costa LJ, Ronald AR, Maitha GM, Gakinya MN, et al. Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet. 1989; 2(8660): 403-7. 7. 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. 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The protective effect of circumcision on HIV incidence in rural low-risk men circumcised predominantly by traditional circumcisers in Kenya: two-year follow-up of the Kericho HIV Cohort Study. J Acquir Immune Defic Syndr. 2007; 45(4): 371-9. 12. Kim AA, Parekh BS, Umuro M, Galgalo T, Bunnell R, Makokha E, et al. Identifying risk factors for recent HIV infection in Kenya using a recent infection testing algorithm: Results from a nationally representative population-based survey. PLoS One. 2016; 11(5): e0155498. 13. Dandona L, Kumar GA, Lakshmi V, Ahmed GMM, Akbar M, Ramgopal SP, et al. HIV incidence from the first population-based cohort study in India. BMC Infect Dis. 2013; 13: 327. 14. Grabowski MK, Serwadda DM, Gray RH, Nakigozi G, Kigozi G, Kagaayi J, et al. HIV prevention efforts and incidence of HIV in Uganda. N Engl J Med. 2017; 377(22): 2154-66. 15. Lissouba P, Taljaard D, Rech D, Dermaux-Msimang V, Legeai C, Lewis D, et al. Adult male circumcision as an intervention against HIV: an operational study of uptake in a South African community (ANRS 12126). BMC Infect Dis. 2011; 11: 253. 16. Auvert B, Taljaard D, Rech D, Lissouba P, Singh B, Bouscaillou J, et al. Association of the ANRS-12126 male circumcision project with HIV levels among men in a South African township: evaluation of effectiveness using cross-sectional surveys. PLoS Med. 2013; 10(9): e1001509. 17. Vandormael A, Akullian A, Siedner M, de Oliveira T, Barnighausen T, Tanser F. Declines in HIV incidence among men and women in a South African population-based cohort. Nat Commun. 2019; 10(1): 5482. 18. Borgdorff MW, Kwaro D, Obor D, Otieno G, Kamire V, Odongo F, et al. HIV incidence in western Kenya during scale-up of antiretroviral therapy and voluntary medical male circumcision: a population-based cohort analysis. Lancet HIV. 2018; 5(5): e241-e9. 19. Kagaayi J, Chang LW, Ssempijja V, Grabowski MK, Ssekubugu R, Nakigozi G, et al. Impact of combination HIV interventions on HIV incidence in hyperendemic fishing communities in Uganda: a prospective cohort study. Lancet HIV. 2019; 6(10): 680-7. 20. Wawer MJ, Makumbi F, Kigozi G, Serwadda D, Watya S, Nalugoda F, et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet. 2009; 374(9685): 229-37. 21. Baeten JM, Donnell D, Kapiga SH, Ronald A, John-Stewart G, Inambao M, et al. Male circumcision and risk of male-to-female HIV- 1 transmission: a multinational prospective study in African HIV-1-serodiscordant couples. AIDS. 2010; 24(5): 737-44. 22. 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. 23. Turner AN, Morrison CS, Padian NS, Kaufman JS, Salata RA, Chipato T, et al. Men’s circumcision status and women’s risk of HIV acquisition in Zimbabwe and Uganda. AIDS. 2007; 21(13): 1779-89. 24. Fatti G, Shaikh N, Jackson D, Goga A, Nachega JB, Eley B, et al. Low HIV incidence in pregnant and postpartum women receiving a community-based combination HIV prevention intervention in a high HIV incidence setting in South Africa. PLoS One. 2017; 12(7): e0181691. 9Web Annex 2.1: GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men Fig. A2.1.2. Rates of severe and moderate adverse events in studies of voluntary medical male circumcision for adolescents and men BOT = Botswana; DOM = Dominican Republic; KEN = Kenya; MOZ = Mozambique; MWI = Malawi; NAM = Namibia; RWA = Rwanda, TZA = United Republic of Tanzania, UGA = Uganda; ZAF = South Africa; ZMB = Zambia; ZWE = Zimbabwe. Source: Jindai K, Awori Q, Farley T, Temu J, Samuelson J. Safety of male circumcision for HIV prevention by conventional surgical methods and age, unpublished; available from WHO/UCN/Global HIV, Hepatitis and STIs Programmes (hiv-aids@who.int). Point estimate Pooled estimate Combined point estimate for all studies 10 Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics References for Figure A2.1.2 1. Krieger JN, Bailey RC, Opeya JC, Ayieko BO, Opiyo FA, Omondi D, et al. Adult male circumcision outcomes: experience in a developing country setting. Urol Int. 2007; 78(3): 235-40. 2. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 Trial. PLoS Med. 2005; 2(11): e298. 3. Kigozi G, Gray RH, Wawer MJ, Serwadda D, Makumbi F, Watya S, et al. The safety of adult male circumcision in HIV-infected and uninfected men in Rakai, Uganda. PLoS Med. 2008; 5(6): e116. 4. Lagarde E, Taljaard D, Puren A, Auvert B. High rate of adverse events following circumcision of young male adults with the Tara KLamp technique: a randomised trial in South Africa. S Afr Med J. 2009; 99(3): 163-9. 5. Kanyago S, Riding DM, Mutakooha E, Lopez de la OA, Siedner MJ. Shang Ring versus forceps-guided adult male circumcision: a randomized, controlled effectiveness study in southwestern Uganda. J Acquir Immune Defic Syndr. 2013; 64(2): 130-3. 6. Mutabazi V, Kaplan SA, Rwamasirabo E, Bitega JP, Ngeruka ML, Savio D, et al. HIV prevention: male circumcision comparison between a nonsurgical device to a surgical technique in resource-limited settings: a prospective, randomized, nonmasked trial. J Acquir Immune Defic Syndr. 2012; 61(1): 49-55. 7. Sokal DC, Li PS, Zulu R, Awori QD, Combes SL, Simba RO, et al. Randomized controlled trial of the shang ring versus conventional surgical techniques for adult male circumcision: safety and acceptability. J Acquir Immune Defic Syndr. 2014; 65(4): 447-55. 8. Tshimanga M, Mangwiro T, Mugurungi O, Xaba S, Murwira M, Kasprzyk D, et al. A Phase II randomized controlled trial comparing safety, procedure time, and cost of the PrePex device to forceps guided surgical circumcision in Zimbabwe. PLoS One. 2016; 11(5): e0156220. 9. Kigozi G, Musoke R, Watya S, Kighoma N, Ssebbowa P, Serwadda D, et al. The acceptability and safety of the Shang Ring for adult male circumcision in Rakai, Uganda. J Acquir Immune Defic Syndr. 2013; 63(5): 617-21. 10. Kigozi G, Musoke R, Watya S, Kighoma N, Nkale J, Nakafeero M, et al. The safety and acceptance of the PrePex device for non- surgical adult male circumcision in Rakai, Uganda. A non-randomized observational study. PLoS One. 2014; 9(8): e100008. 11. Millard PS, Wilson HR, Veldkamp PJ, Sitoe N. Rapid, minimally invasive adult voluntary male circumcision: A randomised trial. S Afr Med J. 2013; 103(10): 736-42. 12. Millard PS, Wilson HR, Goldstuck ND, Anaso C. Rapid, minimally invasive adult voluntary male circumcision: a randomised trial of Unicirc, a novel disposable device. S Afr Med J. 2014; 104(1): 52-7. 13. Kigozi G, Musoke R, Kighoma N, Nkale J, Serwada D, Sewankambo N, et al. The acceptability and safety of the Shang Ring for adolescent male circumcision in Rakai, Uganda (TUPE148). 20th International AIDS Conference; July 20-25, 2014; Melbourne, Australia; (http://www.abstract-archive.org/Abstract/Share/18795). 14. Shenje J, Millard PS. Sutureless adult voluntary male circumcision with topical anesthetic: A randomized field trial of Unicirc, a single-use surgical instrument. PLoS One. 2016; 11(6): e0157065. 15. Ngo TD, Obhai G. Male circumcision uptake, postoperative complications, and satisfaction associated with mid-level providers in rural Kenya. HIV AIDS (Auckl). 2012; 4: 37-43. 16. Phili R, Abdool-Karim Q, Ngesa O. Low adverse event rates following voluntary medical male circumcision in a high HIV disease burden public sector prevention programme in South Africa. J Int AIDS Soc. 2014; 17: 19275. 17. Brito MO, Lerebours L, Volquez C, Basora E, Khosla S, Lantigua F, et al. A clinical trial to introduce voluntary medical male circumcision for HIV prevention in areas of high prevalence in the Dominican Republic. PLoS One. 2015; 10(9): e0137376. 18. Wirth KE, Semo BW, Spees LP, Ntsuape C, Barnhart S, Ledikwe JH. A prospective cohort study of safety and patient satisfaction of voluntary medical male circumcision in Botswana. PLoS One. 2017; 12(11): e0185904. 19. Hove J, Masimba L, Murenje V, Nyadundu S, Musayerenge B, Xaba S, et al. Incorporating Voluntary Medical Male Circumcision into traditional circumcision contexts: Experiences of a local consortium in Zimbabwe collaborating with an ethnic group. Glob Health Sci Pract. 2019; 7(1): 138-46. 20. Buwembo DR, Musoke R, Kigozi G, Ssempijja V, Serwadda D, Makumbi F, et al. Evaluation of the safety and efficiency of the dorsal slit and sleeve methods of male circumcision provided by physicians and clinical officers in Rakai, Uganda. BJU Int. 2012; 109(1): 104-8. 21. Herman-Roloff A, Bailey RC, Agot K. Factors associated with the safety of voluntary medical male circumcision in Nyanza province, Kenya. Bull World Health Organ. 2012; 90(10): 773-81. 22. Frajzyngier V, Odingo G, Barone M, Perchal P, Pavin M. Safety of adult medical male circumcision performed by non-physician clinicians in Kenya: a prospective cohort study. Glob Health Sci Pract. 2014; 2(1): 93-102. 11Web Annex 2.1: GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men 23. Montague C, Ngcobo N, Mahlase G, Frohlich J, Pillay C, Yende-Zuma N, et al. Implementation of adolescent-friendly voluntary medical male circumcision using a school based recruitment program in rural KwaZulu-Natal, South Africa. PLoS One. 2014; 9(5): e96468. 24. Reed JB, Grund J, Liu Y, Mwandi Z, Howard AA, McNairy ML, et al. Implementation and Operational Research: Evaluation of Loss- to-Follow-up and Postoperative Adverse Events in a Voluntary Medical Male Circumcision Program in Nyanza Province, Kenya. J Acquir Immune Defic Syndr. 2015; 69(1): e13-23. 25. Kohler PK, Namate D, Barnhart S, Chimbwandira F, Tippet-Barr BA, Perdue T, et al. Classification and rates of adverse events in a Malawi male circumcision program: impact of quality improvement training. BMC Health Serv Res. 2016; 16: 61. 26. Ngcobo S, Wolvaardt JE, Bac M, Webb E. The quality of voluntary medical male circumcision done by mid-level workers in Tshwane District, South Africa: A retrospective analysis. PLoS One. 2018; 13(1): e0190795. 27. Soboil N, Laube C, Mwinyi A, Rooinasie S, Valombula M. Monitoring adverse events in a new mature male circumcision client cohort in Namibia [WEPEC0909]. IAS, 2017; Paris; (http://programme.ias2017.org//PAGMaterial/eposters/4522.pdf). 28. Lissouba P, Taljaard D, Rech D, Doyle S, Shabangu D, Nhlapo C, et al. A model for the roll-out of comprehensive adult male circumcision services in African low-income settings of high HIV incidence: the ANRS 12126 Bophelo Pele Project. PLoS Med. 2010; 7(7): e1000309. 29. Muquingue H, Ndimande S, Necochea E, Wei S, Frescas R, Malimane I, et al. Profile of adverse events in a national VMMC program in Mozambique (2009 to 2017): Reduction in AE with a national scale-up, but three events require further attention [TUAC0204]. AIDS, 2018; Amsterdam; (http://programme.aids2018.org/Abstract/Abstract/10871). 30. Hellar A, Christensen A, Reed J, Kapula A, Mkungume S, Machaku M, et al. Switching from the forceps-guided to the dorsal slit technique in a Voluntary Medical Male Circumcision (VMMC) program: Experience from Tanzania. 22nd International AIDS Conference, 2018; Amsterdam; (https://programme.aids2018.org/PAGMaterial/eposters/5931.pdf). 31. Feldacker C, Bochner AF, Murenje V, Makunike-Chikwinya B, Holec M, Xaba S, et al. Timing of adverse events among voluntary medical male circumcision clients: Implications from routine service delivery in Zimbabwe. PLoS ONE. 2018; 13(9): e0203292. 12 Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics Ta bl e A2 .1 .3 . G RA DE e vi de nc e pr ofi le : P IC O qu es tio n. A m on g ad ol es ce nt s un de r 1 5 ye ar s, c om pa re d wi th o ld er a do le sc en t b oy s or m en , i s su rg ic al m al e ci rc um ci si on s af e? A ut ho r( s) : T im F ar le y D at e: 2 01 9 Q ue st io n: A m on g ad ol es ce nt s un de r 1 5 ye ar s, c om pa re d w ith o ld er a do le sc en t b oy s or m en , i s su rg ic al m al e ci rc um ci si on s af e? Se tt in gs : V ol un ta ry m ed ic al m al e ci rc um ci si on p ro gr am m es fo r H IV p re ve nt io n Q ua lit y as se ss m en t N o. o f pa ti en ts (n o. o f ev en ts /n o. a t ri sk ) Ef fe ct Q ua lit y Im po rt an ce N o. o f st ud ie s De si gn Ri sk o f b ia s In co ns is te nc y In di re ct ne ss Im pr ec is io n O th er co ns id er at io ns Ag e < 15 y r Ag e ≥ 15 y Re la tiv e (9 5% C I) h Ab so lu te (9 5% CI ) i O ut co m e: m od er at e or s ev er e ad ve rs e ev en ts (a ll ty pe s) 0 M Cs p er fo rm ed in ra nd om iz ed tr ia ls of c irc um ci si on fo r H IV pr ev en tio n a — — — — — — — — — CR IT IC AL 1 1 su rg ic al ci rc um ci si on a rm of M C de vi ce co m pa ra tiv e st ud ie s b — — — — — 0/ 12 7 (0 .0 % ) b — — — CR IT IC AL 3 2- 4 VM M C pr og ra m m es w ith 10 00 – 1 0 00 0 cl ie nt s se rio us ri sk c so m e in co ns is te nc y d so m e in di re ct ne ss e se rio us im pr ec is io n f no ne 15 /7 55 (1 .9 p er 1 00 ) 18 1/ 45 97 (3 .9 p er 1 00 ) 0. 80 (0 .4 8, 1. 35 ) 14 fe w er p er 10 00 (fr om 6 to 2 2 fe w er ) VE RY L O W CR IT IC AL 2 5, 6 VM M C pr og ra m m es w ith at le as t 1 0 00 0 cl ie nt s so m e ris k g no in co ns is te nc y no in di re ct ne ss no im pr ec is io n no ne 81 1/ 40 7 94 4 (0 .2 0 pe r 1 00 ) 12 13 /3 74 7 78 (0 .3 2 pe r 1 00 ) 0. 62 (0 .5 7, 0 .6 8) 1. 2 fe w er p er 10 00 (fr om 1 .0 to 1 .5 fe w er ) LO W CR IT IC AL O ut co m e: m od er at e or s ev er e ad ve rs e ev en ts – in fe ct io ns 1 6 VM M C pr og ra m m es w ith at le as t 1 0 00 0 cl ie nt s so m e ris k g — no in di re ct ne ss no im pr ec is io n no ne 47 /1 9 61 9 (0 .2 4 pe r 1 00 ) 27 /2 5 24 9 (0 .3 2 pe r 1 00 ) 2. 24 (1 .4 0, 3 .6 0) 1. 3 m or e pe r 10 00 (fr om 0 .5 to 1 .2 m or e) LO W CR IT IC AL N ot es a Ag e ra ng es 1 8- 24 y ea rs , 1 7– 28 y ea rs a nd 1 5- 49 y ea rs in th e th re e RC Ts . b Ag e ra ng e 13 –1 7 ye ar s, no A Es in s ur gi ca l M C gr ou p. B re ak do w n of c irc um ci si on s by a ge g ro up n ot g iv en . c O ne s tu dy in K en ya w ith c lin ic al fo llo w -u p vi si t c on du ct ed in c lie nt ’s ho m e if sc he du le d 1 w ee k po st c irc um ci si on c lin ic fo llo w -u p vi si t m is se d fo un d an a dd iti on al 5 2 AE s be yo nd th e 23 A Es id en tifi ed a t c lin ic v is it. U nd er -a sc er ta in m en t o f A Es m ar ke dl y gr ea te r i n cl ie nt s ag e 13 –1 7 ye ar s co m pa re d w ith th os e ag e 18 y ea rs a nd o ld er . d O ve ra ll AE ra te s va rie d co ns id er ab ly b et w ee n st ud ie s. e Ta rg et c om pa ris on b et w ee n ag es 1 0– 14 y ea rs a nd ≥ 1 5 ye ar s – tw o st ud ie s co m pa re d ag e gr ou ps 1 3– 17 y ea rs w ith ≥ 1 8 ye ar s, on e st ud y co m pa re d ag e gr ou ps 1 5– 19 y ea rs w ith ≥ 2 0 ye ar s. f Sm al l n um be r o f e ve nt s an d fe w c lie nt s ag e un de r 1 5 ye ar s. g Re po rt ed A E ra te 1 0- fo ld lo w er th an in s m al le r V M M C pr og ra m m es w ith fa ci lit ie s fo r b et te r m on ito rin g. 13Web Annex 2.1: GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men References for Table A2.1.3 1. Kigozi G, Musoke R, Kighoma N, Nkale J, Serwada D, Sewankambo N, et al. The acceptability and safety of the Shang Ring for adolescent male circumcision in Rakai, Uganda (TUPE148). 20th International AIDS Conference; July 20-25, 2014; Melbourne, Australia; (http://www.abstract-archive.org/Abstract/Share/18795). 2. Frajzyngier V, Odingo G, Barone M, Perchal P, Pavin M. Safety of adult medical male circumcision performed by non-physician clinicians in Kenya: a prospective cohort study. Glob Health Sci Pract. 2014; 2(1): 93-102. 3. Reed JB, Grund J, Liu Y, Mwandi Z, Howard AA, McNairy ML, et al. Implementation and Operational Research: Evaluation of Loss- to-Follow-up and Postoperative Adverse Events in a Voluntary Medical Male Circumcision Program in Nyanza Province, Kenya. J Acquir Immune Defic Syndr. 2015; 69(1): e13-23. 4. Soboil N, Laube C, Mwinyi A, Rooinasie S, Valombula M. Monitoring adverse events in a new mature male circumcision client cohort in Namibia [WEPEC0909]. IAS, 2017; Paris; (http://programme.ias2017.org//PAGMaterial/eposters/4522.pdf). 5. Muquingue H, Ndimande S, Necochea E, Wei S, Frescas R, Malimane I, et al. Profile of adverse events in a national VMMC program in Mozambique (2009 to 2017): Reduction in AE with a national scale-up, but three events require further attention [TUAC0204]. AIDS, 2018; Amsterdam; (http://programme.aids2018.org/Abstract/Abstract/10871). 6. Bochner AF, Feldacker C, Makunike B, Holec M, Murenje V, Stepaniak A, et al. Adverse event profile of a mature voluntary medical male circumcision programme performing PrePex and surgical procedures in Zimbabwe. J Int AIDS Soc. 2017; 19(1): 21394. 14 Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics Table A2.1.4. Evidence-to-decision-making: male circumcision for HIV prevention Recommendation: Voluntary medical male circumcision (VMMC) should continue to be promoted as an additional efficacious HIV prevention option within combination prevention for adolescent boys 15 years and older and for adult men in settings with generalized epidemics to reduce the risk of heterosexually acquired HIV infection. Factor Explanation/evidence Judgment Quality of evidence High quality, consistent evidence over diverse range of study types including three randomized controlled trials Strong Balance of benefits versus harms Preventing heterosexually acquired HIV infection • Efficacy is partial but consistent and lifelong. • Impact in communities was noted, including alongside scale-up of antiretroviral treatment (ART). • VMMC intervention remains necessary to achieve epidemic control even in the context of other current efficacious prevention intervention options and ART scale-up in East and Southern Africa. • Impact among women is indirect, with possible direct effect after wound healing. Other benefits • Circumcised men and their female partners experience lower rates of several sexually transmitted infections, including human papillomavirus, herpes simplex virus type 2, bacterial vaginosis and Trichomonas vaginalis, than uncircumcised men and their female partners. • Women benefit indirectly, from the lower risk of HIV infection in circumcised men as VMMC programmes expand and fewer men acquire HIV. • Women may be somewhat less likely to acquire HIV infection from an HIV- positive man who is circumcised than from one who is not. Other issues addressed • Traditional male circumcision may be undertaken in collaboration with the formal health sector providing the surgical procedure, thus reducing risk with traditional circumcision methods. Harms • Severe and moderate adverse events and rates were reportedly low, but adverse events do occur, which requires that clients understand risks and benefits. • No evidence noted of increases in risky sexual behaviours (risk compensation), including less condom use or more partners, but education on safer sexual behaviour is essential with provision of VMMC. • If a man who has HIV wants circumcision, he should be on ART prior to undergoing circumcision, both for his own health and to reduce his HIV viral load and, thus, transmission risk during the healing period. In high HIV burden settings, particularly East and Southern Africa, benefits greatly outweigh harm. Values and preferences • HIV prevention and risk reduction: valued by programmes in high burden countries and donors for its contribution to preventing HIV and associated burden and its potential to reach men for other health care interventions such as screening and treatment for noncommunicable diseases. • Limited information on values of preventing HIV from the perspective of men and women; some information on older men in East and Southern Africa indicated that higher priority concerns are livelihood, food, sex. • One qualitative process evaluation of a sports-based intervention noted that older men (over 30 years) reported a lack of motivation for circumcision because HIV testing and VMMC would make little difference at their age. Due to limited evidence, it is not possible to assess if there are any important uncertainties and variabilities in the importance of VMMC for HIV prevention. The Guideline Development Group considered the health burden of HIV, including its social implications, to be large. It is important to implement effective interventions that help people to avoid this burden. Resource use VMMC is cost-effective and in many settings cost-saving within the next 5–10 years. Strongly in favour Equity and human rights • A few studies were identified that address equity. Traditional community values are a key factor directly affecting the acceptability of VMMC, thus indirectly affecting equity. Those who live in communities where VMMC is not supported have been adversely affected in terms of equity. In one study in Tanzania, people who resided in remote locations, farther than 5 km and, even more so, farther than 10 km from a fixed VMMC facility, were likely to be disadvantaged for post-VMMC follow-up. • As a one-time intervention, reduction in risk will continue over a lifetime. • VMMC must be provided in line with human rights, ethical and legal considerations, including high quality information for communities, women and men; informed voluntary consent; and high quality, safe services that are monitored for adverse outcomes. • VMMC should be provided only as part of a combination prevention package. Equity favours the one-time intervention to permanently reduce heterosexual HIV risk in men. Ethics and human rights are essential. The overall ethical justification for VMMC as a public health initiative is dynamic and depends on a number of different factors that can change over time, including the emergence of new HIV prevention modalities, epidemiological changes, new data about safety and new approaches to voluntary informed consent. Feasibility • Scaling up to 23 million men circumcised between 2008 and 2018 demonstrates feasibility in many settings. – This scale-up occurred mostly using a vertical approach with donor support. However, integrated approaches showed positive outcomes towards sustaining services. – Challenges and barriers faced in scaling up are specific to context and population. – Global efforts now underway to scale up adolescent services and essential and emergency surgical services present opportunities for synergies. The Guideline Development Group considered VMMC a feasible intervention and favoured a recommendation recognizing the need for sufficient resource capacity. 15Web Annex 2.1: GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men Factor Explanation/evidence Judgment Acceptability of VMMC intervention Men, women, community leaders, programmes, policy • To date over 23 million VMMCs have been performed, demonstrating acceptability. • Age disaggregation demonstrated higher acceptability among adolescents and lower acceptability among older men, although evidence on adolescent or parental acceptability was limited. • Regional and cultural differences in acceptability. • Main drivers of acceptability were reduction in risk of HIV and STIs and improved hygiene. VMMC considered acceptable in high HIV burden settings, with recognition of variation by age and culture. Table A2.1.4. (continued) 16 Preventing HIV through safe voluntary medical male circumcision for adolescent boys and men in generalized HIV epidemics Table A2.1.5. Evidence-to-decision-making: offer of VMMC to younger adolescent boys (ages 10–14 years) Factor Explanation/evidence Judgment Balance of benefits versus harms Benefits of lifetime HIV and STI prevention versus harms of potentially higher frequency of severe adverse events (SAE), including some rare events with possible long-term consequences, in the younger age adolescent boys (10–14 years) were the main factors considered. These considerations are based on limited evidence of SAE risk and uncertainties about future HIV incidence. Benefits. Biological effectiveness of VMMC in reducing heterosexually acquired HIV is expected to be the same for younger adolescents as among those circumcised above age 15 years (“older adolescents”). Risk of other STIs also reduced. Less risk of HIV acquisition during healing period in younger adolescents, as they are less likely to be sexually active. Faster healing among younger adolescents than among older adolescents. Harms. The frequency of glans injuries was greater among younger adolescents (particularly those whose genitalia were less mature) compared with adolescents 15 years and older; however, some uncertainty exists regarding the magnitude of excess risk based on adverse event data available. All reported cases of glans injury and 98% of urethral fistula cases occurred among those under 15 years. Uncertainty exists regarding the potential harms of bullying/stigmatization when circumcision in a younger adolescent is deferred until more physically mature. Other. May be advantageous to provide VMMC services package to adolescents at a later developmental stage, when they can better understand HIV prevention and sexual and reproductive health (SRH) information and education. Overall, need to improve safety monitoring, including disaggregation by narrower age bands and by stage of sexual maturity. Uncertainty regarding balance between benefits compared with possible harms. Better safety data are needed. Age is used as a proxy for physical maturity. But the age when adolescents reach physical maturity varies. Therefore, some flexibility is needed rather than deciding by age alone. The offer of VMMC to younger adolescents depends on their capacity to provide fully informed consent. Values and preferences No evidence from literature on relative values and preferences for safety or on maintaining VMMC coverage for a particular age group of adolescents. The Guidelines Development Group noted: • the importance of HIV as a public health burden; thus, there is a need to maintain high coverage. • Some adolescents are sexually active before the age of 15 years. No judgment possible Acceptability of male circumcision at younger adolescent ages Evidence on acceptability by boys and parents comes only from limited studies, which consistently show high acceptability by parents/mothers and fathers for circumcision of sons, including at younger adolescent ages (<14 years). Social norms have changed in East and Southern Africa since the initial 2007 recommendation, with programmatic evidence suggesting that VMMC for this age group is acceptable. About 45% of the VMMCs since 2015 have been for adolescents ages 10–14. Community context must be considered also. Some health care providers noted that it is not possible to provide meaningful SRH education to younger adolescents. Several barriers and facilitators to implementing VMMC for younger adolescent were reported, with pain the most commonly mentioned barrier to acceptability and HIV protection the most commonly cited facilitator. Convenient timing (for example, after school terms) increases acceptability. Although the Guidelines Development Group favoured prioritization of VMMC for adolescents whose genitalia are mature, evidence overall suggests that VMMC may be acceptable for younger adolescent boys and their parents if concerns about pain and peri- and post-procedural care are weighed against the benefits of HIV prevention. If a national programme decides to include younger adolescents, it must put in place the necessary precautions to ensure the safety of those adolescents not yet physically mature and/or not yet having the capacity to consent. VMMC for younger adolescents seems acceptable, but limited evidence is available for this age group. Resource use Conclusions from two references: • VMMC is a one-time intervention that results in lifelong benefits for the individual and community. • Most males ages 10–14 years are not sexually active. Thus, there is a time lapse before they benefit from VMMC. Although cost-effectiveness modelling suggests that VMMC in boys ages 10–14 years may not be a programme priority, turning them away would mean refusing services to some (varies by country) clients accessing VMMC services and could be viewed by implementers as a likely missed opportunity, given less demand for VMMC to date among older males. Inclusion of other services has not been assessed in terms of efficiencies or effectiveness, but the opportunity to provide other recommended services, such as tetanus toxoid-containing vaccination booster, prevention education and other locally relevant interventions could increase cost-effectiveness and impact. Resource use is uncertain, as multiple factors not taken into account beyond the cost of VMMCs per HIV infection averted. 17Web Annex 2.1: GRADE and evidence-to-decision tables on voluntary medical male circumcision for HIV prevention among adolescents and men Factor Explanation/evidence Judgment Equity and ethics • No evidence from the literature • Age of consent for surgical procedures varies by country. • International human rights standards encourage postponing a non- emergency, invasive and irreversible procedure until the adolescent is sufficiently mature to provide his informed consent. Evolving capacity has a bearing on independent decision-making, such that some younger adolescents may be able to provide consent. • If national programmes offer VMMC to younger adolescents who do not yet have the capacity to consent, assent from minors should be obtained as well as parental/guardian consent that is provided on the day of surgery. A human rights-based approach calls for a fair opportunity to access VMMC services. Ethics calls for ensuring consent or, if offered to a minor, assent along with consent of parent/guardian. Feasibility • ≈50% of VMMCs have been performed in adolescents <19 years, with a varying percentage among 10–14 year olds. • As this age group is seeking health care services, guidance is needed on how to manage the younger adolescents and their parents when VMMC is not offered. Need to consider providing other services and follow-up to support clients returning later for VMMC. • Evidence points to the need for improvements in provider training and better counselling of younger males and for adolescent-specific counselling guidelines (for example, on condom use and on HIV counselling in general and specific to disclosing HIV-positive test results to younger clients). • Tools to assess physical maturity are not readily available, and health care workers would need adequate training to correctly assess physical maturity. (Physical maturity is not equivalent to cognitive maturity or capacity to consent.) • Need to address issues regarding timing (vis-à-vis school and exams) and to engage with parents. • VMMC is an important opportunity to provide adolescent boys with information and counselling on SRH issues, but HIV testing services may not be needed for the youngest clients. Although providing VMMC to younger adolescents is feasible (as evidenced by the experience to date of programmes, which have provided VMMC to a large number of younger adolescents), there are uncertainties regarding the feasibility of how to deliver VMMC and other services to younger adolescent boys and providers’ capacity to assess their physical and cognitive capacity. Table A2.1.5. (continued) For more information, contact: World Health Organization Global HIV, Hepatitis and STIs Programmes 20, Avenue Appia 1211 Geneva 27 Switzerland E-mail: hiv-aids@who.int https://www.who.int/hiv/pub/malecircumcision/en/