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Characteristics of Women Enrolled into a Randomised Clinical Trial of Dapivirine Ring for HIV-1 Prevention Nyaradzo Mgodi (MBChB, MMed) UZ-UCSF Annual Research Day 17 April 2015 Background • Over half of the 24.7 million people living with HIV-1 infection in sub-Saharan Africa in 2013 were women . • Unprotected heterosexual intercourse is the leading mode of HIV-1 transmission amongst women in this region. • Randomized trials of the antiretroviral agent tenofovir, formulated as oral pills or a topical vaginal gel, demonstrated efficacy in diverse at-risk populations worldwide. • However, in two trials among young women at risk for HIV-1 (VOICE and FEM-PrEP), adherence to daily tenofovircontaining pills or vaginal gels was very low and HIV-1 prevention efficacy could not be assessed. Background • To quote Dr Hunidzarira from this morning “An HIV vaccine is the world’s best hope of ending HIV” • However, the world may be facing 20 million to 60 million new HIV infections in the 15 to 20 years it may take to develop and evaluate a vaccine that protects against HIV infection • In the interim, in order to protect women, development of potent, antiretroviral-based prevention products not requiring daily or coitally-dependent adherence is a priority. • Products like the Dapivirine Intra-vaginal ring Dapivirine Intra-vaginal Ring • Dapivirine is a non-nucleoside reverse transcriptase inhibitor • Flexible ring made of an elastic silicone material • Measures 56 mm (about 2 ½”) in diameter and 7.7 mm (3/4”) thick • Designed for 28-day use • International Partnership for Microbicides (IPM) providing both the placebo ring and the dapivirine ring for the study MTN-020 / ASPIRE A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase III Safety and Effectiveness Trial of a Vaginal Matrix Ring Containing Dapivirine for the Prevention of HIV-1 Infection in Women (ClinicalTrials.gov number NCT01617096). A Study to Prevent Infection with a Ring for Extended Use MTN-020 Objectives • Primary Objective – To determine the effectiveness and safety of dapivirine (25 mg) administered in a silicone elastomer vaginal matrix ring, when inserted once every 4 weeks, in preventing HIV-1 infection among healthy sexually active HIV-1 uninfected women • Secondary Objectives – To assess the acceptability of and adherence to the dapivirine vaginal ring, the frequency of drug resistance, and the relationship between drug concentrations and HIV-1 seroconversion MTN-020 Design • Randomized, placebo-controlled, double-blind, phase III trial • Sexually active HIV-1 uninfected women who are non-pregnant, contracepting, and between 18-45 years of age • HIV-1 testing, risk reduction, contraceptive provision, safety monitoring, pregnancy testing, product provision, adherence counseling • Ring worn for 4 weeks, replaced every 28-35 days • All participants receive a comprehensive HIV-1 prevention package including risk-reduction, condoms, treatment of STIs, and partner testing and referral services ASPIRE: 2,629 women, 15 sites, 4 countries Blantyre Lilongwe Malawi (272 women) – 10% Cape Town Durban (7 sites) Johannesburg South Africa (1,426 women) – 54 % Kampala Uganda (253 women) – 10% Harare/Chitungwiza (3 sites) Zimbabwe (678 women) - 26% Participant Characteristics Malawi South Africa Uganda Zimbabwe All Countries Participants enrolled, N 272 (10%) 1426 (54%) 253 (10%) 678 (26%) 2629/5516 Age, years (median, IQR) 28 (24, 33) 24 (21, 29) 28 (24, 33) 28 (25, 33) 26 (22, 31) Currently unmarried 41 (15%) 1313 (92%) 87 (34%) 112 (17%) 1553 (59%) 9 (3%) 3 (0.2%) 9 (4%) 2 (0.3%) 23 (1%) Primary school (partial and complete) 140 (51%) 46 (3%) 117 (46%) 78(12%) 381 (14%) Secondary school (partial and complete) 121 (44%) 1245 (87%) 112 (44%) 592 (87%) 2070 (79%) 2 (1%) 132 (9%) 15 (6%) 6 (1%) Highest level of education No schooling Attended college or university 155 (6%) Baseline Contraceptive Use Malawi South Africa Uganda Zimbabwe All Countries Intrauterine device 6 (2%) 79 (6%) 71 (28%) 169 (25%) 325 (12%) Oral contraceptives 6 (2%) 242 (17%) 14 (6%) 18 (3%) 280 (11%) Injectable contraceptives 115 (42%) 1046 (73%) 112 (44%) 179 (26%) 1452 (55%) 120 (44%) 21 (1%) 49 (19%) 311 (46%) 501 (19%) 25 (9%) 42 (3%) 7 (3%) 3 (0.4%) 77 (3%) Current method of contraception Hormonal implant Sterilization STIs Detected at Screening Malawi South Africa Uganda Zimbabwe All Countries Trichomonas vaginalis 28 (10%) 88 (6%) 13 (5%) 51 (8%) 180 (7%) Neisseria gonorrhoeae 13 (5%) 55 (4%) 15 (6%) 26 (4%) 109 (4%) Chlamydia trachomatis 6 (2%) 237 (17%) 25 (10%) 48 (7%) 316 (12%) Syphilis 11 (4%) 7 (0.5%) 15 (2%) 39 (1%) STIs detected at the screening visit 6 (2%) Timeline Sept 2012 •Protocol implementation June 2014 •Completion of accrual July 2015 •Completion of follow-up visits Dec 2015 •ASPIRE results Q2/Q3 2016 •HOPE Implementation •To again quote - Dr Kangwende from this morning: “We are Christians, we continue to MTN-025 Timeline ASPIRE results HOPE (MTN-025) opens Dec 2015 RA/IRB/EC informed Former Participants contacted Participants informed National and community Stakeholders informed HOPE (MTN-025) approval and site activation Enrollment 6 months Up to 1-year open-label use of dapivirine ring Thank you • • • • • • • Participants, partners and research communities CAB Members Chitungwiza City Health Department ZNFPC UZ-CHS Staff at Seke South, Spilhaus, Zengeza CRSs UZ-UCSF The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes