Transcript Are You Ready for the ARV Revolution? Transforming HIV Prevention September 14, 2011 Jim Pickett Director of Prevention Advocacy and Gay Men’s Health AIDS Foundation of.

Are You Ready for
the ARV Revolution?
Transforming HIV Prevention
September 14, 2011
Jim Pickett
Director of Prevention Advocacy and Gay Men’s Health
AIDS Foundation of Chicago
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Today
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Definitions
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•
•
•
ARV, ART, HAART
Microbicide
PrEP
Treatment
– Treatment as Prevention
– TLC+
– TNT
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1000+
advocates,
Mission:
support
scientists,
funders,
development
of
policymakers
from 6
safe, effective,
continents –and
S.
acceptable,
America/Latin
accessible
America
and Nigeria
rectal microbicides
for all chapters
that need them
AFC secretariat
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rectalmicrobicides.org
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Highly active moderated listserv, website, blog, Facebook, Twitter, teleconferences
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English, Spanish, French, Russian and Chinese
rectalmicrobicides.org
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Condoms work.
So why do we need new strategies to
halt the sexual transmission of HIV?
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Here are some reasons for new strategies
Source: Roger Tatoud PhD, Senior Programme Manager, International HIV Clinical Trials Research Mgmt Office,
Imperial College London
&
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IRMA Steering Committee Member
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And here are some more
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Source: Measure Evaluation. 1997–2002. http://www.measuredhs.com
What if we had a complete prevention tool kit?
Prior to exposure
•Rights-focused
behaviour change
•Voluntary counselling
and testing
•STI screening and
treatment
•Male medical
circumcision
•Preventive Vaccines
•Pre-exposure
prophylaxis (PrEP)
Point of transmission
•Male and female
condoms and lube
•ARV treatment to
prevent vertical
transmission (PMTCT)
•Clean injecting
equipment
•Post-exposure
prophylaxis (PEP)
•Vaginal and rectal
microbicides
Treatment
• Improved ARV therapy
• Treatment for
opportunistic infections
• Basic care/nutrition
• Prevention for positives
• Education & rights-focused
behaviour change
• Therapeutic vaccines
ARV = antiretroviral
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The prevention landscape
has forever changed
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Let’s review the science
CAPRISA 004
iPrEx
FEM PrEP
HPTN 052
Partners PrEP
TDF2 (CDC 4940)
Shall we?
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CAPRISA 004 – July 2010
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South Africa 2 sites in
KwaZulu-Natal
Phase IIB - 889
HIV- women,
18 – 40
Enrolled May
2007 – Jan.
2009
Vaginally
formulated
tenofovir gel
Results July
20, 2010 –
AIDS 2010
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iPrEx – November 2010
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*Only about half the
men took their pills
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New data on iPrEx
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New data on iPrEx
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Fem PrEP – 2011
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But what about FEM PrEP?
• Phase III, multi-center, double-blind,
randomized, placebo-controlled
effectiveness and safety study to assess the
role of Truvada in preventing HIV acquisition
in women
• 1,951 women Kenya, South Africa, Tanzania
• Study discontinued April – futility
– HIV infection endpoints: 56 (78% of 72)
– Truvada arm: 28, Placebo arm: 28
• Final data Q4 2011
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HPTN 052 – 2011
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HPTN 052
• Results first released May, “official” at IAS
• Phase III clinical trial to eval effectiveness
of ART to prevent sexual transmission of
HIV in serodiscordant couples
• Two study arms
– 1) immediate initiation of ART in HIV-infected
partner upon enrollment
– 2) delayed initiation ART in HIV-infected
partner until 2 consecutive CD4 cell counts
were at or below 250 t-cells or AIDS-defining
illness
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HPTN 052
• 1,763 HIV serodiscordant couples
enrolled between April ‘05 – May ‘10
– 886 couples randomly assigned immediate
ART arm
– 877 were randomly assigned delayed ART
arm
• Malawi, Zimbabwe, Botswana, Kenya,
South Africa, Brazil, Thailand, US, India
• 97% of the partnerships heterosexual
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HPTN 052
• Early initiation ART led to 96% reduction
in HIV transmission to HIV- partner
• 105 morbidity and mortality events noted,
with 40 in immediate ART arm, and 65 in
delayed ART arm, showing trend toward
benefit favoring immediate arm
• Among endpoints, 3 extra-pulmonary
tuberculosis events in immediate, and 17
in delayed
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HPTN 052
This is the first randomized clinical trial to
definitively indicate that an HIVinfected individual can reduce sexual
transmission of HIV to an uninfected
partner by beginning antiretroviral
therapy sooner.
– Myron Cohen, PI
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Partners PrEP – 2011
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Partners PrEP
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•
•
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Tenofovir, Truvada, placebo
HIV-serodiscordant couples
Once daily dosing
4,758 HIV-serodiscordant couples
– 60% couples male HIV-, 38% couple female HIV-
• Kenya, Uganda
• University of Washington, Bill & Melinda
Gates Foundation, Gilead Sciences
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Partners PrEP
• Overall: TDF = 62% reduction, FTC/TDF
= 73%
– TDF efficacy
– 68% fem, 58% men vs. placebo
– FTC/TDF efficacy
– 62% fem, 83% men vs. placebo
• All differences “not statistically
significant”
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Partners PrEP
• High adherence – 97% across all arms
– Self reports correlate with pill count
– Higher in couples?
• No significant safety concerns
• Recently closed placebo arm
– Placebo arm offered either
– Active drug arms remain blinded
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Partners PrEP
This is an extremely exciting
finding for the field of HIV
prevention. Now, more than
ever, the priority for HIV
prevention research must be on
how to deliver successful
prevention strategies, like PrEP,
to populations in greatest
need.
–Dr. Jared Baeten, study co-chair
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TDF2 (CDC 4940) – 2011
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TDF2 (CDC 4940)
• Bostwana – 1,219 neg het men/women aged
18 – 39 (46% women)
• Once-daily dosing Truvada vs. placebo
• 63% overall efficacy
• 78% overall efficacy if only counting people
who had been to clinic in last month
• Adherence by pill count – 84%
• No significant safety concerns
• All offered open label
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TDF2 (CDC 4940)
These are exciting results for global
HIV prevention. We now have
findings from two studies showing
that PrEP can work for
heterosexuals, the population
hardest hit by HIV worldwide. Taken
together, these studies provide
strong evidence of the power of this
prevention strategy.
– Kevin Fenton, director CDC National Center
for HIV/AIDS, Viral Hepatitis, STD, and TB
Prevention
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Trials underway
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VOICE/MTN 003
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VOICE/MTN 003
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VOICE/MTN 003
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VOICE/MTN 003
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FACTS 001
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Overview of FACTS 001
• FACTS 001 will be similar to CAP004.
• It is designed as a confirmatory study
and is placebo controlled.
• Study will test BAT24 dosing of
tenofovir gel.
• A minimum of 2,200 women will be
enrolled at 9 sites across South Africa.
• Study will enroll young HIV-negative
women aged 18-30.
• Study scheduled to start in
Sept./October and last around 2 and
half years.
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PrEP studies underway
CDC 44370
Once-daily
tenofovir
2,400 HIVnegative injecting
drug users (IDUs)
Thailand
(Bangkok)
Results 2012
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PrEP studies underway
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Rectal snapshot
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RM research activities
• Baseline studies
– What normally happens during AI?
• Formulation studies
– How will different chemicals and substances be
put together to make a safe, effective RM?
• Distribution studies
– Where do RMs need to go?
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RM research activities
• Acceptability & behavioural studies
– What kinds of products would people use?
– Who is having AI?
• Pre-clinical/basic science
– developing and testing products in labs and in
animal studies
• Clinical trials – safety and efficacy
– Are these RMs safe? Do they work?
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The RM pipeline is flowing
• RMP 01 – UC-781
• 36 U.S.
• MTN 006 – tenofovir • 18 U.S.
• MTN 007 – modified
tenofovir
• 60 U.S., 3 sites
• Project Gel underway • 120/42 U.S., Puerto Rico
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MTN 017
• 180 Peru, RSA, Thailand,
U.S.
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Preview of MTN O17
• Protocol still in development (may change)
– First Phase II trial in the field
• “Phase 11 Randomized, Expanded Rectal Safety and
Acceptability Study of Reduced Glycerin Tenofovir 1%
Gel and Truvada”
– 2 arms
» 8wks daily oral Truvada, week off, 8 wks daily gel
» 8wks gel, week off, 8wks daily oral Truvada
• Target start date early 2012
• Thailand, Peru, South Africa, US (Boston, Pitt)
• Gay men, MSM, transgender women
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Populations for RM studies
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Acceptability of RMs
• iPrEx – Only 50% of men took their pills
regularly, if at all
• An ARV-based prevention option based on
a lubricant or an enema could be more
acceptable to these men
• Three Phase I studies completed
• Phase II – MTN 017 – coming
• Buffet approach!
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They work…
Now
what?
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Mapping Pathways
• Conceived as two-year project – India, RSA, U.S. focus
• Partners in India, RSA, UK and U.S.
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–
–
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Community engagement
Naz India, Desmond Tutu HIV Foundation
AIDS United, AIDS Foundation of Chicago
RAND Europe – research, literature review
Baird’s CMC – communications/project management support
• Goals:
– To develop and nurture a research-driven, community-led global
understanding of the emerging evidence base around the adoption of
antiretroviral-based prevention strategies to end the HIV/AIDS
epidemic.
– To provide the research and analysis that communities and
policymakers need in order to formulate coherent, evidence-based
decisions for HIV/AIDS treatment and prevention strategies in the 21st
century.
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Interviews: interesting glimpses from South Africa
• TLC+
– A quantum leap.
– South African pathologist
– It’s not going to happen. You can’t do it .
– South African researcher
– Financial sustainability in this context is unlikely.
– South African activist
– Keeping patients well is always a good thing financially.
– South African pathologist
– The programme will pay for itself.
– South African pathologist
– Forget about CD4 counts and put everyone on treatment.
– South African epidemiologist
– If you have cancer, the doctor doesn’t say, “Let’s wait until you’re halfdead til we give you treatment.”
– South African epidemiologist
– You’ve got to look for acute infections, otherwise you’d
just be doing a half-hearted job.
– South African researcher
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N = 11
Interviews: interesting glimpses from South Africa
• PrEP
– The iPrex and FEM-PEP results left us wondering.
– South African researcher
– PreP has been hopelessly oversold with people going on and on as if
it’s the holy grail.
– South African clinician
– In our country, where people are dying of AIDS every day – until we
deal with them, we can’t do this. They are a higher priority.
– South African policy-maker
– People are used to taking pills.
– South African policy-maker
– Can see a justification for implementing PrEP in high risk groups.
– South African activist
– A nightmare.
– South African activist
– A waste of money.
– South African policy-maker
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N = 11
Interviews: interesting glimpses from South Africa
• Microbicides
– May work, but we need more data.
– South African epidemiologist
– We don’t yet have a topical microbicide that is highly effective.
– South African epidemiologist
– Once we get convincing scientific evidence.
– South African activist
– Potential for much greater, proper use and less risk.
– South African activist
– It will be easier to do than drugs.
– South African policy-maker
– Difficult to apply.
– South African pathologist
– I can’t see anyone who would use them.
– South African clinician
– People are more likely to use them.
– South African activist
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Interviews: interesting glimpses from South Africa
• Political will
– The philosophical argument is essentially won on a
scientific level and increasingly on a political level.
– South African epidemiologist
– Behind the curve but they’re coming round.
– South African epidemiologist
– The AIDS Directorate is really looking at TLC+ as an option.
– South African pathologist
– No doubt an enormous desire to focus on prevention, and rightly so.
–South African policy-maker
– Policy-makers don’t look at the future.
– South African researcher
– Policy-makers are not just interested in HIV.
– South African researcher
– There is a low readiness to implement.
– South African activist
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PrEP public health response CDC
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CDC steps
MMWR [Morbidity & Mortality Weekly Report]
• Review trial data, interim guidance for physicians*
U.S. Public Health Service guidelines
Identifying the most effective mix of interventions
Avoiding increases in risk behaviors
Cost, access
Continuation of PrEP research
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CDC interim guidance
Close
consultation
with doctor
Wait for full
guidelines
Daily dosing
critical
Initial and
regular testing
Only obtained
from doctor
Truvada only
– nothing
else proven
Only if
confirmed
HIV-negative
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PrEP public health response CDPH
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Advantages
• Minimal side effects
• Convenience
• Effectiveness
Disadvantages
• Resistance
• Behavioral
Cost
• PrEP estimated $14,400/yr (varies by source and
attendant services)
• Annual cost of ARV for POZ = $24,000 +/CDPH
• Intervention not forever
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Demo projects, advocacy
projectinform.org
lifelube.blogspot.com
Letter from HIV+ gay men
rectalmicrobicides.org
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There aint no mountain high enough
Aint no valley low enough
Aint no river wide enough
“IF YOU THINK YOU’RE TOO SMALL TO MAKE
A DIFFERENCE, YOU’VE NEVER SPENT THE
NIGHT WITH A MOSQUITO.”
– AFRICAN SAYING
Questions?
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Thank you
And thank you to AVAC, MTN, FACTS, iPrEx, Deb Baron, Sharon Hillier, Mike Chirenje,
Ian McGowan, Bob Grant, Roger Tatoud, Marc-Andre LeBlanc
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Don’t be a stranger
[email protected]
rectalmicrobicides.org
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