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 tenofovir containing 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

Participants enrolled, N Age, years (median, IQR) Currently unmarried Highest level of education

No schooling Primary school (partial and complete) Secondary school (partial and complete) Attended college or university

Malawi South Africa Uganda

272 (10%) 1426 (54%) 253 (10%)

Zimbabwe All Countries

678 (26%) 2629/5516 28 (24, 33) 24 (21, 29) 28 (24, 33) 28 (25, 33) 26 (22, 31) 41 (15%) 1313 (92%) 87 (34%) 112 (17%) 1553 (59%) 9 (3%) 2 (1%) 3 (0.2%) 140 (51%) 46 (3%) 132 (9%) 9 (4%) 117 (46%) 121 (44%) 1245 (87%) 112 (44%) 15 (6%) 2 (0.3%) 23 (1%) 78(12%) 381 (14%) 592 (87%) 2070 (79%) 6 (1%) 155 (6%)

Current method of contraception

Intrauterine device Oral contraceptives Injectable contraceptives Hormonal implant Sterilization

Baseline Contraceptive Use

Malawi South Africa Uganda Zimbabwe All Countries

6 (2%) 79 (6%) 71 (28%) 169 (25%) 325 (12%) 6 (2%) 242 (17%) 14 (6%) 18 (3%) 280 (11%) 115 (42%) 1046 (73%) 112 (44%) 179 (26%) 1452 (55%) 120 (44%) 21 (1%) 25 (9%) 42 (3%) 49 (19%) 311 (46%) 501 (19%) 7 (3%) 3 (0.4%) 77 (3%)

STIs Detected at Screening

Malawi South Africa Uganda Zimbabwe All Countries STIs detected at the screening visit

Trichomonas vaginalis Neisseria gonorrhoeae Chlamydia trachomatis Syphilis

28 (10%) 88 (6%) 13 (5%) 51 (8%) 180 (7%) 13 (5%) 55 (4%) 15 (6%) 26 (4%) 109 (4%) 6 (2%) 11 (4%) 237 (17%) 25 (10%) 48 (7%) 316 (12%) 7 (0.5%) 6 (2%) 15 (2%) 39 (1%)

Sept 2012

Timeline

• Protocol implementation June 2014 • Completion of accrual July 2015 Dec 2015 • Completion of follow-up visits • 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

Dec 2015

RA/IRB/EC

informed

HOPE

(MTN-025)

opens

Participants

informed National and community

Stakeholders

informed

HOPE (MTN-025) approval and site activation Former Participants

contacted

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 of Health.