Transcript Microbicides 2008

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
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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