Transcript Convergence in the scientific agendas across the HPTN, MTN

Current and planned HIV
prevention trials:
microbicides and PrEP
Presented at:
XVIII International AIDS Conference, Vienna, 22 July 2010
Salim S. Abdool Karim
Pro Vice-Chancellor (Research): University of KwaZulu-Natal
Director: CAPRISA
Professor 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 trials
Trial
CDC Bangkok
tenofovir trial
iPREX trial
PartnersPrEP trial
VOICE
FemPrEP
Product
Target
population
Sites
Viread
2,400 IDUs
Thailand
Truvada
3,000 MSM
Peru, Ecuador, US,
S Africa and Brazil
Viread &
4,700 discordant
Truvada
couples
Tenofovir gel,
Viread &
5,000 women
Truvada
Viread &
Truvada
3,900 women
Kenya, Uganda
Malawi, South Africa,
Uganda, Zambia,
Zimbabwe
Kenya, Malawi,
South Africa,
Tanzania, Zambia
Available for download from: http://www.sciencemag.org/sciencexpress/recent.dtl
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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
HIVNET 012 - nevirapine
12 hrs
Study
asap
72 hrs
PMTCT - HIVNET 012
41
Tenofovir gel - CAP 004
39
asap
54
Tenofovir gel – high adherence
Tenofovir gel – medium adherence
38
Tenofovir gel – low adherence
28
CAPRISA 004 tenofovir gel
0%
10
20
30
40
50
60
Efficacy
70
80
90 100%
PrEP trials being planned
Trial
IPM 009
Product
Dapivirine ring
Target
population
TBD
MDP 302
Tenofovir gel
Women
South African
tenofovir gel trial
Tenofovir gel
Women
Sites
TBD
South Africa,
Uganda,
Kenya
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?