Developing HIV Prevention Options for Women: Microbicides (Martin Methot)
Current and planned HIV prevention trials: microbicides and PrEP
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Transcript of Current and planned HIV prevention trials: microbicides and PrEP
Current and planned HIV prevention trials:
microbicides and PrEPPresented at:
XVIII International AIDS Conference, Vienna, 22 July 2010
Salim S. Abdool KarimPro Vice-Chancellor (Research): University of KwaZulu-Natal
Director: CAPRISAProfessor in Clinical Epidemiology, Columbia University
Adjunct Professor of Medicine, Cornell University
Outline Why the interest in PrEP? Historical overview of PrEP research Current PrEP trials Summary of the CAPRISA 004 findings Planned PrEP trials Key challenges in the implementation of
PrEP trials Conclusion
Pre-exposure prophylaxis (PrEP) Pre-exposure prophylaxis (PrEP) is an experimental
HIV prevention strategy that uses antiretroviral agents prior to exposure, to prevent HIV acquisition
PrEP for HIV prevention builds on the concept that medications can be used by healthy people to prevent other infections:• Mefloquine prophylaxis for malaria• INH prophylaxis for tuberculosis
Mathematical modeling impact: 2.7 - 3.2 million new HIV infections could be averted in southern Africa in 10 years by targeting PrEP (if 90% effective) to those at highest behavioral risk
Source: Abbas UL, PLoS ONE 2(9): e875. doi:10.1371/journal.pone. 0000875
Why the interest in PrEP…. Biological plausibility – effect of ARVs
on viral replication Numerous animal challenge since
since 1995 show protection Success of post-exposure prophylaxis
for needlestick exposure in observational data
pMTCT: Proof of concept via another route of transmission in humans
Initial efforts to test PrEP:Tenofovir PrEP studies halted by activists
At what cost? How many infections could have been prevented if these trials went ahead?
Tenofovir PrEP trial stopped due to low HIV incidence in study populations in
Ghana, Cameroon and Nigeria
Botswana PrEP trial stopped due to low HIV incidence & mobile populations
Current PrEP trialsTrial Product Target
population Sites
CDC Bangkok tenofovir trial Viread 2,400 IDUs Thailand
iPREX trial Truvada 3,000 MSM Peru, Ecuador, US, S Africa and Brazil
PartnersPrEP trial Viread & Truvada
4,700 discordant couples Kenya, Uganda
VOICETenofovir gel,
Viread & Truvada
5,000 womenMalawi, South Africa,
Uganda, Zambia, Zimbabwe
FemPrEP Viread & Truvada 3,900 women
Kenya, Malawi, South Africa,
Tanzania, Zambia
12Available for download from: http://www.sciencemag.org/sciencexpress/recent.dtl
Summary of CAPRISA 004 findings• Safety
No substantive safety concerns No tenofovir resistance identified Safe in Hepatitis B virus infected women No evidence of risk compensation / behavioral disinhibition
• Proof of concept that tenofovir gel can prevent HSV-2 infection in women 51% reduction in HSV-2
• Proof of concept that tenofovir gel can prevent HIV infection in women 39% protection against HIV overall 50% reduction in HIV after 1 year of tenofovir gel use 54% effective in women with high adherence
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Comparison of HIV effectiveness: HIVNET 012 and CAPRISA 004
Efficacy
StudyPMTCT - HIVNET 01241
Tenofovir gel – high adherence54
Tenofovir gel – low adherence28
Tenofovir gel - CAP 00439
0% 10 20 30 40 50 60 70 80 90 100%CAPRISA 004 tenofovir gel
HIVNET 012 - nevirapineasap
72 hrs12 hrs
asap
Tenofovir gel – medium adherence38
PrEP trials being planned
Trial Product Target population Sites
IPM 009 Dapivirine ring TBD TBD
MDP 302 Tenofovir gel WomenSouth Africa,
Uganda, Kenya
South African tenofovir gel trial Tenofovir gel Women South Africa
Key challenges in future implementation of PrEP: impact on study design
Is it safe to give ARV drugs to healthy people?
Will those who get infected have HIV that is resistant to the PrEP antiretrovirals? Will this affect their subsequent care and choice of ARV treatment?
Will healthy people be willing to take medication everyday or at the time of sex for long periods?
Is this an affordable and practical HIV prevention strategy for scale-up if it is efficacious?
Will there be behavioural disinhibition / risk compensation?
Conclusion Oral and topical PrEP – promising & results awaited Current trials: tenofovir gel/pill and truvada pill in:
• IDUs, discordant couples, young women, MSM If effective, implementation programs will require
extensive community education to promote PrEP with integrated use of other prevention strategies
The provision of PrEP will require integration into existing HIV prevention and health care services
Need to include long term follow-up and surveillance in sentinel groups to monitor adverse events, adherence, drug resistance, impact of drug resistance on later AIDS treatment and behavioural disinhibition
Future questions for PrEP Which drug? Which formulation (oral or topical)?
Which dosing strategy? What impact on adherence, efficacy and safety
Do long-acting formulations such as vaginal rings or slow release bolus dosing impact on adherence and risk of drug resistance?
Are combinations of ARVs better in terms of safety, efficacy and drug resistance?
Should an ARV (or class) be set aside for PrEP?