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AIDS 2010: Proof-of-concept that an antiretroviral can prevent HIV infection CAPRISA 008 Tenofovir Gel Implementation Trial Good Adherence in Trial of Topical Pre-Exposure Prophylaxis Integrated into Family Planning Services Dr Leila E Mansoor (PhD) * Co-Principal Investigator * on behalf of the CAPRISA 008 team AIDS 2016 – Durban, South Africa – 22 July 2016 Introduction • WHO recommended the roll-out of pre-exposure prophylaxis (PrEP) to reduce HIV transmission in populations at substantial risk. • In Africa, a key target for PrEP implementation is young women, the group at highest risk. • However, PrEP efficacy is highly variable in this group: VOICE Trial: -49% (95% CI: -129 to 3) for daily oral TDF Botswana TDF2 trial: 75% (95% CI: 24 to 94) for daily oral TDF/FTC. • Product effectiveness in “real-world” settings can also differ markedly from product efficacy observed in clinical trials. • Limited data exist, beyond clinical trials, to guide the introduction of PrEP in health care services. • Many young women utilize existing family planning (FP) services – presents an opportunity for introducing PrEP as part of their established sexual and reproductive health (SRH) services. Study summary • Purpose: To assess adherence and effectiveness of topical PrEP (tenofovir gel) integration into FP services – while simultaneously providing post-trial tenofovir gel access to CAPRISA 004 women • Design: Open-label, 2-arm, randomized controlled, noninferiority trial (conducted between 2012 – 2015) • Population: HIV-uninfected women who previously participated in the CAPRISA 004 trial • Measurements: Demographics – Sex acts – Applicator counts – Adherence – Clinic retention – HIV incidence – Service preference Intervention and control groups Control arm: CAPRISA trial clinics with monthly provision & monitoring of tenofovir gel – similar to the CAPRISA 004 clinical trial Intervention arm: Public sector FP services with 2-3 monthly provision & monitoring of tenofovir gel The use of Quality Improvement (QI) methodology to promote reliable service delivery. Two-step approach: QI used to strengthen FP services to be better prepared for expansion QI framework used to assist FP services to add tenofovir gel provision to current SRH service Study consort Eligible for CAPRISA 008: 786 Pre-screened: 716* (91.1%) Screened: 448 (56.9%) Enrolled: 382 (48.6%) Vulindlela: 266 73 (9.3%) could not be contacted 268 (37.4%) were excluded • 52 not interested in participation • 51 had relocated • 48 were working / studying • 47 were HIV positive • 38 did not return for screening visit • 12 were not traceable • 11 were pregnant or planning a pregnancy • 4 had died • 5 other reason 66 (14.7%) were excluded • 37 did not return timeously • 20 were HIV positive • 6 were not sexually active • 2 were pregnant • 1 was co-enrolled in another trial eThekwini: 116 * This includes 3 participants who were screened for CAPRISA 008 in error ; 1 was screened out and 2 were enrolled Study consort …cont. Enrolled: 382 FP service: 193 4 were excluded • 2 were HIV positive • 2 co-enrolled in another trial Analysed: 189 15 did not complete the study • 10 refused further participation • 4 were lost to follow-up • 1 withdrawn from study Trial clinic: 189 6 were excluded • 4 were HIV positive • 1 no post-randomization follow-up • 1 pregnant at enrolment Analysed: 183 16 did not complete the study • 9 refused further participations • 3 were lost to follow-up • 1 withdrawn from study • 2 died • 1 relocated Completed study: 174 (92.1%) Completed study:167 (91.3%) Retention: 92.1% Retention: 92.3% Selected baseline characteristics --- similar between FP service and trial clinics --Variable FP service (N=189) Trial clinic (N=183) 29.5; ±5.8; 20-44 1.6; ±1.1; 0-8 78 (41.3) 98 (51.9) 13 (6.9) 182 (96.2) 29.3; ±5.3; 22-44 1.5; ±1.0; 0-5 78 (42.6) 92 (50.3) 13 (7.1) 172 (93.9) 0.741 0.451 0.973 3; ±2.5; 1-25 6; ±6.7; 0-72 1/188 (0.5) 35/187 (18.7) 65 (34.4) 95 (50.3) 29 (15.3) 3; ±2.7; 1-20 6; ±5.9; 0-38 2/183 (1.1) 38/183 (20.8) 78 (42.6) 86 (47.0) 19 (10.4) 0.745 0.970 0.619 0.695 0.163 p-value Socio-demographic characteristic Age (mean;±SD; range) Parity (mean;±SD; range) Education level (n,%): Didn’t complete high school High school completed Tertiary education initiated Hormonal contraception (n,%) * 0.223 Sexual behavioural characteristics Total lifetime sex partners (mean;±SD; range) Sex acts: past 30 days (mean;±SD; range) Anal sex: past 30 days (n/N,%) Living with regular partner (n/N,%) Male condom use (n,%): Always Sometimes Never * Hormonal contraception includes depo-provera [222 (59.7%)], oral [75 (20.1%)], nur-isterate [56 (16.6%)], and implants [1 (0.25%)] Quarterly retention rates Target: 90% per annum --- similar between FP service and trial clinics --- Adherence, drug levels & HIV incidence --- similar between FP service and trial clinics --FP service (N=189) (95% CI) Trial clinic (N=183) (95% CI) 5.2 (4.7 - 5.7) 3.6 (3.2 – 4.1) 79.9% (76.7 – 83.2) 6.0 (5.5 - 6.5) 4.5 (4.0 – 5.0) 73.9% (70.7 – 77.1) Adherence Mean returned used applicators per month Mean number of sex acts per month Mean adherence [gel/(sex x2)] Mean difference Drug levels (N=313) % with detectable drug levels at 12 months Risk ratio % with detectable drug levels when sex is reported within 7 days % with detectable drug levels when no recent sex is reported HIV incidence HIV incidence per 100 women years Incidence rate ratio 5.92% (1.5 to 10.6) 39.5% (32.2 -47.3) 43.6% (36.1 – 51.4) 0.91 (0.70 to 1.18) 81/139 (58.3%) 49/174 (28.2%) 3.5 (1.8 – 6.0) 3.6 (1.9 – 6.3) 0.96 (0.40 to 2.35) Higher adherence (mean difference = 5.92% [CI: 1.5-10.6]) in FP service clinics met the pre-defined non-inferiority criteria. HIV incidence in an age-comparable historical CAPRISA 004 placebo control group Incidence rate (95% CI) in CAPRISA 008 Incidence rate (95% CI) in women of comparable age from CAPRISA 004 Difference: IRR ratio (95% CI) 3.5 (2.3-5.2) 6.2 (CI 3.5-8.9) Difference: -2.7 IRR: 0.56 Overall HIV incidence rate was 44% lower than that observed in an age-comparable historical placebo-control group from the CAPRISA 004 Tenofovir Gel trial Preference for receiving HIV prevention Private general practitioner Public PHC/FP clinic Mobile clinic Doesn’t want to use study product Missing Other * Total (N=372) N (%) FP service (N=189) N (%) Trial clinic (N=183) N (%) 27 (7.3) 280 (75.3) 6 (1.6) 1 (0.3) 12 (3.2) 46 (12.4) 11 (6.0) 147 (80.3) 5 (2.7) 0 (0.0) 6 (3.2) 20 (10.9) 16 (9.0) 133 (75.1) 1 (0.6) 1 (0.6) 6 (3.3) 26 (14.7) * Other = CAPRISA Clinic (44), pharmacy (1), a place that opens on weekends (1) In summary • At baseline women assigned to FP service and trial clinics were similar. • During the study four critical markers were similar between the FP service and trial clinics: Retention rates (92.1% vs 92.3%) Adherence – estimated as the proportion of reported sex acts covered by two gel doses ( 79.9% vs 73.9%) Genital tenofovir levels at month 12 (39.5% vs 43.6%) • Genital tenofovir was detected in 58.3% of 139 women reporting sex within 7 days but only in 28.2% of 174 women reporting no recent sex. HIV incidence rates (3.5 per 100 wy vs 3.6 per 100 wy) • HIV incidence rate was 44% lower than HIV incidence in an agecomparable historical CAPRISA 004 placebo control group (3.5 vs 6.2 per 100 wy). • Most women (75.3%) expressed a preference for receiving HIV prevention from FP service clinics. Conclusion • Integration of PrEP into FP services is feasible, acceptable and can achieve good adherence, similar to those achieved in clinical trial settings. • While some of the behaviors related to PrEP may be formulation dependent, this study provides broadly applicable information on – the motivation of women to initiate PrEP, maintain follow-up, and adhere to tenofovir-containing HIV prevention in FP clinic services. • This clinical trial evidence may be helpful to policy makers and health care providers planning on implementing oral PrEP scale-up. Acknowledgements • Financial support: USAID (USA & SA) through CONRAD The South African Government’s Department of Science & Technology (DST) through the Technology Innovations Agency (TIA) M-A-C AIDS fund through the Tides Foundation • Trial oversight committee: CAPRISA: Q Abdool Karim, SS Abdool Karim, LE Mansoor USAID (US): D Stanton, L Claypool, M Barnhart USAID (Pretoria): A Thambinayagam, V Francis CONRAD: J Schwartz, G Doncel DST/TIA: S Gumbi, G Loots, M Selematsela, J Coates M-A-C AIDS/Tides: N Mahon, A Flynn, R Burman Gilead Sciences: J Rooney • Tenofovir & placebo gel: Provided by CONRAD & Gilead Sciences • FHI 360: K Torjesen, M Chen • IHI: K Mate, P Barker, M Tshabalala, N Mobisson-Etuk • CONRAD regulatory support: A Spagnoli