K. Jean , P. Lissouba , D. Taljaard , R. Rain- Taljaard , B. Singh, J. Bouscaillou ,

1. Melbourne – July, 25th 2014 HIV incidence among women is associated with their partners' circumcision status in the township of Orange Farm, South Africa(ANRS-12126) K. Jean, P. Lissouba, D. Taljaard, R. Rain-Taljaard, B. Singh, J. Bouscaillou, G. Peytavin, R. Sitta, S.G. Mahiane, D. Lewis, A. Puren, B. Auvert Inserm CESP U1018, Villejuif, France Université Versailles Saint-Quentin-en-Yvelines, Versailles, France CHAPS, Johannesburg, South Africa National Institute for Communicable Diseases, Johannesburg, South Africa

2. 2 Introduction- The effect of VMMC roll-out on HIV amongwomen Background – The effect of VMMC on HIV among men • 3 RCTsdocumenting a protective effect of VMMC among men • Recommended by WHO-UNAIDS since 2007 • Effect of roll-out demonstratedamong men (Auvert et al, Plos Med 2013) An effect on HIV amongwomen? • No direct effectobserved in epidemiologicalstudies (Weiss et al, Lancet ID 2009) • An indirect effectthroughreducedexposure? • Predicted by modellingstudies (Williams et al, Plos Med 2006; Njeuhmeli et al, Plos Med 2011) VMMC: Voluntary Male MedicalCircumcision RCT: RandomizedControlled Trial

3. 3 Objective • To assess the association betweentheirpartner’scircumcisionstatusand HIV incidenceamongwomen in Orange Farm (South Africa) Context- The ANRS « BopheloPele » project • Orange Farm: Township of ~110,000 adults • Since 2007: roll-out of free VMMC ORANGE FARM VMMC: Voluntary Male MedicalCircumcision

4. 4 Context(2) - The ANRS « BopheloPele » project • MC prevalenceincreasedfrom 11% in 2007 to 53% in 2011 Auvertet al, Plos Med 2013

5. 5 Context(3) - The ANRS « BopheloPele » project • HIV prevalencereduced by ~50% amongcircumcised men Auvertet al, Plos Med 2013

6. 6 Methods (1)– Surveys Data collectedamongwomen: 3 independantsurveys (2007-2010-2012) • Questionnaire: age, ethnic group, religion, occupation, age at first sexual intercourse, alcoholconsumption, education, everhaving been married, number of lifetimepartners,consistent condom use • Blood sample: HIV Pooledsample • N= 4538 women(15-49 y)havingeverhadsexual intercourse

7. 7 Methods (2):Modelling HIV incidence fromobservedage-specificprevalence • 3 steps in the modellingprocess • 1.Assuming a parametricage-incidence function • 2.Calculatingage-specificprevalencefromparametric incidence • 3.Fitting the predicted age-specificprevalence to the observedage-specificprevalence → Estimating the incidence parameters → Estimatingincidence rate → Computing 95% confidence interval (Bootstrap) • A classical mathematical deterministic compartmental modeling approach (Gregson et al, AIDS 1996; Williams et al, Stat Med 2001) • Finding the age-incidence functionthat best fits theobservedage-prevalencecurve • Use of propensity score weigthingto account for othercovariates: • survey, age, ethnicgroup, religion, occupation, age at first sexual intercourse, alcoholconsumption, education, everhaving been married, number of lifetimepartners,consistent condom use

8. 8 Results(1) – HIV prevalenceamongwomen • n=1363 (30.0%) womenhaving • hadonlycircumcisedpartners (HHOCP) • HIV prevalence rate : 22.4% [20.2% - 24.6%] N= 4538 women(15-49 y)havingeverhadsexual intercourse • n=3175 (70.0%) otherwomen • HIV prevalence rate : 36.6% [35.0% - 38.3%] aPRR: 0.85 [0.76-0.95] Reduction: 15% 2[5%-24%] aPRR: adjustedPrevalence Rate Ratio (computedwith Poisson regression)

9. 9 Results(2)– Fittingage-specific HIV prevalence Women HHOCP: n=1363 Otherwomen: n=3175 HHOCP: HavingHadOnlyCircumcisedPartners

10. 10 Results(3)– Estimating HIV incidence Normal line: Women HHOCP Bold line: Other women (95% bootstrapped confidence intervals) Women HHOCP: n=1363 Otherwomen: n=3175 HHOCP: HavingHadOnlyCircumcisedPartners

11. 11 Results(4)– Effect on HIV incidence Normal line: Women HHOCP Bold line: Other women (95% bootstrapped confidence intervals) Women HHOCP: n=1363 • Incidence rates among 15-49 y • WomenHHOCP: 0.032 [0.027-0.037] /py • OtherWomen: 0.039 [0.036-0.042] /py • Incidence Rate Ratio: 0.83 [0.69-0.99] • Reduction: 16.9% [1.1%-31.0%] • Among 15-29 y • Reduction: 20.3% [5.8%-33.8%] Otherwomen: n=3175 HHOCP: HavingHadOnlyCircumcisedPartners

12. 12 Discussion • Main finding • Reduced HIV incidence amongwomenhavingonlycircumcisedpartners • Interpretation • Lower exposure due to a lower levelof HIV amongcircumcisedmen • Limitations • Direct or indirect effect? • HIV incidence modelled, not measured

13. 13 Overview of results on VMMC roll-out obtained in Orange Farm (2007-2014) • Among men • VMMC uptakecanberapid and large • VMMC isnot statisticallyassociatedwith condom use • Circumcised men have a lowerrisk of prevalent HIV infection • Circumcisedmen have a lowerrisk of incident HIV infection (BED assay) • Amongwomen • Most womenare in favor of VMMC • Most womenprefercircumcised men • Partner’scircumcisionstatusisnot statisticallyassociatedwith condom use • Womenhavingonlycircumcisedpartners have a lowerrisk of lowerrisk of prevalent HIV infection • Womenhavingonlycircumcisedpartners have a lowerrisk of incident HIV infection (modelled) Auvertet al, Plos Med 2013 Auvertet al, CROI 2014; AIDS 2014 VMMC: Voluntary Male MedicalCircumcision

14. Aknowledgments Fikile Kate BongiweKlaas Paul Loubet VenessaMaseko Audrey Mkhwanazi Bantu Mupompa Cynthia Nhlapo Grace NomsaNhlapho Portia Ntshangase Josephine Otchere-Darko Dino Rech ThabileSekhukhune Daniel Shabangu GaphSiphoPhatedi Yvon de la Soudière Brian Williams Muhammad Barmania Scott Billy Alexandre Blake Male Alina Chakela Ewalde Cutler Sasha Frade Agenda Gumbo Mohamed Haffejee We thank all participants who took part in this study and the whole community of Orange Farm