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. . Shorai. . Mukaka. , . MBchB. (. UZ). 05 MAY 2017. Outline. Background. HPTN 082 study. MTN 034 study. IMPAACT 2009 study. Background. There has been global progress in HIV management in the last decade, however, the epidemic remains uncontrolled.. ID: 720415

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ADOLESCENT PrEP STUDIES

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ADOLESCENT
PrEP
STUDIES
Shorai
Mukaka
,
MBchB
(
UZ)
05 MAY 2017
Outline
Background
HPTN 082 study
MTN 034 study
IMPAACT 2009 study
Background
There has been global progress in HIV management in the last decade, however, the epidemic remains uncontrolled.
It exerts an especially high toll in sub‐Saharan Africa, where women and young women are up to twice as likely to be infected as young men.
There has been a rise in the total population of young men and women in Africa since the beginning of the epidemic
In 2015, the youth population made up close to 20% of the continent’s population, and is expected to more than double by 2055
.
(
United
Nations, Department of Economic and Social affairs, Population Division. Youth population trends and sustainable development. May 2015. Population Facts No. 2015/1).
Rates of HIV in young women remain unacceptably high, and hence there is need to target this population in order to curb the epidemic
Demographic Shift in Southern Africa in10-29 year olds
HIV Prevention interventions
There are a number of proven HIV prevention interventions
More HIV prevention strategies are under research
Of the proven methods, some require the participation or consent of a male partner which presents operational challenges in the provision of HIV prevention strategies to young women.

Education
Condoms
Treatment of HIV+
PrEP
Vaccine
Testing
PEP
PrEP
Microbicide
HIV prevention interventions
The FDA approved
Truvada
for oral
PrEP
in 2012.
In 2014, the World Health Organization (WHO) developed recommendations for offering oral
PrEP
containing the antiviral drug
tenofovir
disoproxil
fumarate (TDF), alone or in combination with emtricitabine (FTC), to select key populations at high risk of HIV infection. The WHO further expanded these recommendations in 2015 to include all persons at high risk of HIV infection.Since then, a number of countries, Zimbabwe included, have adopted the WHO guidelines on oral PrEP and incorporated them into their national guidelines
PrEP
WHO guidelines
Substantial risk = incidence rate of
>
3.0 per 100 person-years
HIV prevention interventions
The expansion of the WHO recommendations’ scope was supported by mounting evidence that oral
PrEP
regimens containing TDF, when followed consistently, were safe, cost-effective, and highly efficacious in reducing HIV infection
risk. However
, there is limited data on safety, adherence, and acceptability of
PrEP
for adolescent and young adult females living in high-risk regions, like, sub-Saharan Africa when compared with data collected on other populations
A Phase IV randomized multi-site prospective
feasibility study
to assess
PrEP
acceptance and adherence among HIV-uninfected young women who are offered open-label daily oral
PrEP
with adherence support
0
Primary
Objectives
To
assess the proportion and characteristics of young HIV-uninfected women who accept versus decline
PrEP
at
enrollment
.
To assess the difference in
PrEP
adherence in young women randomized to the enhanced (using drug level feedback) versus standard of care adherence support
1
Secondary Objectives
Timing of
PrEP
acceptance among women who initially decline
PrEP
at
enrollment
but elect to accept
PrEP
during follow up.
Correlates of early and delayed acceptance of
PrEP.
Adverse events and HIV incidences Proportion who discontinue PrEP, timing, & factors associated with PrEP discontinuation
2
Eligibility: select inclusion criteria
16-25
Mobile phone (w/SMS)
VOICE risk score
Sexually active
HBV uninfected and willing to receive HBV vaccine if susceptible to HBV
HIV negative
Interest in
PrEP
(HPRM)
3
Study summary
The study is being conducted at 3 sites African sites including
Spilhaus
.
(
Spilhaus
Clinic, Zimbabwe, the
Emavundleni
Research Centre in Cape Town, South Africa and Wits RHI in Johannesburg, South Africa
HIV-uninfected women ages 16-25
400 young women who accept
PrEP at enrollment and up to 200 young women who decline
PrEP at enrollment. 12 months of follow-up per participant.
4
5
Behavioral data collection
CASI (Partnership characteristics, partner’s HIV status, HIV risk
perception,study
participation disclosure
etc
)
Qualitative interviews (25 per site, 75 total) done at weeks 13 and 26
-Factors that influence women’s uptake and Adherence of
PrEP
-Experience among those randomized to get drug
level feedback
6
Study progress
Regulatory application and stakeholder engagement
Activation- 14 Nov 2016
First Sreening-17 November 2016
First Enrollment-08 December 2016
As of 03 May-136 Screened
-80 Enrolled
We plan to complete accrual by May/Jun 2017
Last follow up Jun/Jul 2018
Results are expected shortly thereafter
7
MTN 034
Reversing the Epidemic in Africa with Choices in HIV Prevention
8
MTN 034
A Phase 2a Crossover Trial Evaluating the Safety of and Adherence to a Vaginal Matrix Ring Containing
Dapivirine
and Oral
Emtricitabine
/
Tenofovir
Disoproxil
Fumarate
in an Adolescent and Young Adult Female Population
9
Rationale
Results from two Phase 3 safety and efficacy trials of the
dapivirine
VR, MTN-020 (ASPIRE) and IPM 027 (The Ring Study) found the VR to be safe and effective in reducing HIV-1 infection.
In The Ring Study,
dapivirine
VR use reduced the risk of HIV-1 infection by 30.7% relative to placebo, and a 37.5% reduction in HIV-1 infection was observed in a subgroup analysis of women
olderthan
21 years
of age
.
0
Rationale
In ASPIRE,
dapivirine
VR use resulted in a 27% relative reduction in HIV-1 incidence overall, a 37% reduction in an analysis defined early in the study excluding data from two study sites with lower retention and adherence, and a 56% reduction in a post-hoc analysis among women older than 21 years of age.
HIV-1 protection was not observed for women aged 18-21, and objective markers of adherence were lower in this subgroup compared to women older than 21. More recent analyses of ASPIRE results presented at the 2016 International AIDS Conference in Durban, South Africa suggest the
dapivirine
VR may lead to reductions in HIV-1 incidence of 56%-65% when used consistently, and may even be as high as 75%-92% for perfect ring use.
The low effectiveness and adherence results observed among young women in The Ring Study and ASPIRE make it clear that gaps still exist in our understanding of how best to incorporate the
dapivirine
VR into the HIV-1 prevention toolkit for this population
1
Study population and design
Healthy, HIV-uninfected, sexually active adolescent and young adult females, 16 - 21 years old (inclusive)
60 participants
per
site
open-label, multi-site, two-sequence, crossover, randomized trial
Approximately 73 weeks of follow-up per participant
2
Study design
Participants will be randomized (1:1) to one of two sequences of a
monthly
dapivirine
24 weeks and
daily
oral
truvada
tablets
taken
for 24 weeks. After completing the randomized sequence of two study product use periods, participants will then select between the two study products to use in the final 24 weeks of the trial. Participants will be able to choose either or neither study product every 4 weeks during the third product use period.
3
Period 1(24 Weeks)
Period 2(24 Weeks)
Period 3(24 Weeks)Sequence A
Vaginal (dapivirine 25 mg VR) Oral Daily FTC/ TDF tablet) Free choice (dapivirine 25 mg VR or daily FTC/TDF tablet) or neither
Sequence BOral (Daily FTC/ TDF tablet)Vaginal (dapivirine 25 mg VR)Free choice (dapivirine 25 mg VR or daily FTC/TDF tablet) or neither
4
Primary objectives
Safety
• To compare the safety profiles of FTC/TDF oral tablet administered daily and
dapivirine
vaginal matrix ring (25 mg) inserted once every 4 weeks during the first 24 weeks of use of each study product in an adolescent and young adult female population
Adherence
• To compare adherence to the FTC/TDF oral tablet administered daily and to the
dapivirine
vaginal matrix ring (25 mg) inserted once every 4 weeks during the first 24 weeks of use of each study product in an adolescent and young adult female population
5
Other objectives
Acceptability
Study product preference
Vaginal Microenvironment
HIV Incidence
6
Timelines
Study is going through regulatory submissions
Activation expected in
Q32017
Accrual planned to end Q3 2018
To complete follow up in 2020 then results shortly thereafter
7
IMPAACT 2009
Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for Primary HIV Prevention during Pregnancy and Breast Feeding in Adolescents and Young Women
A protocol in
development
8
There are currently few interventions being implemented to help women to
remain HIV-free during pregnancy, breastfeeding and beyond. More effort is
needed to address this gap. This may be particularly important for adolescent
women, who may have less experience with and information about HIV.
UNAIDS Gap Report 2014
9
Primary Objectives
To characterize
PrEP
adherence among HIV-uninfected women aged 16-24 years who initiate once-daily TDF-FTC from <32 weeks to 6 months
postpartum
To compare maternal and infant adverse events (including pregnancy outcomes) between women who initiate
PrEP
and those who decline
PrEP
0
Secondary Objectives
To identify individual, social, and structural barriers and facilitators to
PrEP
uptake during
pregnancy
To compare reported sexual risk behavior and incidence of sexually transmitted infections between the
PrEP
and non-
PrEP
cohorts
To compare HIV incidence in women between the two
cohortsTo compare HIV drug resistance in HIV-infected mothers and infants from the two cohorts
1
Study Population
HIV uninfected women
Pregnant
Aged 16-24 years
At risk of
acquiring
HIV
Sample size 350 in total (~100 in Zimbabwe)
Malawi, South Africa, South Africa and Uganda will also take part
2
Study Design
Cohort study, no randomisation
Women will
choose
to start PrEP in pregnancy (~200) or not (~100)
They can change their mind later
Study visits every month x 3, then every 3 months until 6 months after delivery
All get SMS messages about general health matters
PrEP users also get SMS adherence messages and have drug levels tested in near real time
3
4
Study endpoints
Adherence
Tenofovir
disoproxil
fumarate
-diphosphate (TFV-DP) levels measured through dried blood spots.
Safety (maternal and infant)
Adverse pregnancy outcomes will include a composite of the following:Stillbirth
Birthweight <2500 g
Preterm delivery of less than 37 weeks gestationMaternal AE outcome will be a composite of the following:Grade 3 or higher signs and symptoms
Grade 2 or higher chemistry abnormalitiesGrade 3 or higher pregnancy-related diagnosis Pregnancy?
5
Acknowledgements
We sincerely thank our participants, YCAB
, UZ-UCSF staff , our funders and
stakeholders: Zimbabwe National Family Planning Council, Ministry of Health and Child Care, Harare City Health Department, Ministry of Higher and Tertiary
Education.