Transcript Beyond Condoms: Research and Advocacy on New HIV Prevention Technologies March 10, 2012 Positive Living Conference Fort Walton Beach, FL Jim Pickett Director of Prevention Advocacy.

Beyond Condoms: Research and Advocacy on
New HIV Prevention Technologies
March 10, 2012
Positive Living Conference
Fort Walton Beach, FL
Jim Pickett
Director of Prevention Advocacy and Gay Men’s Health , AIDS Foundation of Chicago
Chair, International Rectal Microbicide Advocates
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Today
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Definitions
•
•
•
•
•
ARV, ART, HAART
Microbicide
PrEP
Vaccine
Treatment
– Treatment as Prevention
– TLC+, TNT, TasP
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IRMA, b.2005
4 people, 4 agencies, 2 countries
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1100+
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
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Highly active moderated
listserv, website, blog,
Facebook, Twitter,
teleconferences
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Whether you
use douches,
or not…
TAKE IT.
English, Spanish, French, Portuguese, Thai 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
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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Let’s review the science
CAPRISA 004
iPrEx
FEM PrEP
HPTN 052
Partners PrEP
TDF2 (CDC 4940)
VOICE
Vaccines
Shall we?
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**
As of February 2012
2010
1
2005
Oral
TDF
Oral
TDF/
FTC
2
3
2012
2011
4
1
2
3
4
1
2
3
4
1
2
3
4
Partners PrEP
2009
VOICE/MTN 003
2007
TDF2/CDC 4940
Partners PrEP (no placebo)
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4
1
2
3
4
Arm stopped
Regulatory
submission/filing
2007
iPrEx
2009
FEM-PrEP
2009
2
Positive efficacy
result
TDF2 Open-Label Extension
iPrEx Open-Label Extension (OLE)
Planned
Final results
pending
Oral TDF
Oral TDF/FTC
US FDA filing and decision
TFV
gel
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Bangkok Tenofovir Study/CDC 4370
2008
2007
2015
2014
2013
CAPRISA 004
CAPRISA 008
TFV gel
Rectal TFV gel
DPV ring
VOICE/MTN 003
FACTS 001
FACTS 002 (adolescents)
Rectal
TFV
gel
DPV
ring
Earliest regulatory
submission
MTN 017
The Ring Study/IPM 027
ASPIRE/MTN 020
* Trial end-dates are estimates; due to the nature of clinical trials the actual dates may change. For full trial details, see www.avac.org/trials.
** Not all trials included are effectiveness trials. Trials included on this list are mainly phase II/IIb, III/IIIb and IV trials.
Earliest
regulatory
submission
HIV Prevention is Big News!!
HPTN 052 Study
iPrEX Study of PrEP in MSM
Slide courtesy Dr. Sharon Hillier, MTN
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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2,499 HIV-negative gay, MSM
Brazil, Ecuador, Peru, South Africa,
Thailand, US
Daily Truvada (FTC/TDF
iPrEx – November 2010
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*92% efficacy
among men
with detectable
drug levels
*Only about half the
men took their pills
Conclusions: iPrEX
• Moderate efficacy with daily oral FTC-TDF in MSM
• Drug levels correlate well with efficacy; indicate need
high adherence for high efficacy
– Overestimation of adherence in iPrEX based on pill counts and
participant reports
• No resistance detected in 100 who acquired HIV infection
after enrollment (by standard sequencing)
– 3 cases of resistance in 10 seroconverters at entry (RNA+, Ab-),
8 on placebo and 2 on FTC/TDF
Slide courtesy Dr. Sharon Hillier, MTN
Fem PrEP – 2011, 2012
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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
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Partners PrEP – 2011
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Partners PrEP
•
•
•
•
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
• Closed placebo arm
– Placebo arm offered either
– Active drug arms remain blinded
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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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Trials underway
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VOICE (MTN 003) Design
5,000 Women
Tablet
(3,000)
Truvada
(1,000)
Tenofovir
(1,000)
Vaginal Gel
(2,000)
Placebo Tablet
(1,000)
Tenofovir Gel
(1,000)
Placebo Gel
(1,000)
Slide courtesy Dr. Sharon Hillier, MTN
VOICE has already found oral tenofovir tablets and tenofovir gel were safe
but not effective in the women in those groups.
VOICE continues to test the safety and effectiveness of oral Truvada tablets .
VOICE stopped testing
tenofovir gel after a
17 November 2011
interim review of study
data found tenofovir
gel not effective in the
women in VOICE.
VOICE stopped testing oral
tenofovir tablets after a
16 September 2011 interim
review of study data
determined the tablets were
not effective in VOICE.
5,000 Women
Tablet
(3,000)
Truvada
(1,000)
Tenofovir
(1,000)
Vaginal Gel
(2,000)
Placebo Tablet
(1,000)
Tenofovir Gel
(1,000)
Placebo Gel
(1,000)
Slide courtesy Dr. Sharon Hillier, MTN
13. How could tenofovir gel not be effective in VOICE when the CAPRISA 004 study found it was?
The CAPRISA 004 study found tenofovir gel was 39 percent more effective than placebo when used before and
after sex, a finding that was considered a major milestone for the field. At the same time, it is important to
consider the study’s demographics and the results for what they are. The CAPRISA 004 study involved 889
women, who were all from KwaZulu-Natal, South Africa, and coming from just one study and involving a
single population, the result was not considered strong enough, especially for supporting possible product
licensure. And while the 39 percent level of effectiveness was the result mostf o ten referenced, it’s important to understand that the study also found that the true
level of effectiveness of tenofovir gel – when used
before and after sex – could be anywhere between 6
and 60 percent.
Why Different Outcomes?
• Complex picture
– Different
study questions,
Of the 889 women in CAPRISA 004, 98 women
acquired HIV during the study – 60 women in the
populations
placebo gel group and 38 in the tenofovir gel group.
This means that there were 39 percent fewer
– Same product
infections among those assigned to use tenofovir gel
compared to those in the placebo gel. Because 39
percent is a figureanswers
that represents only an estimate of
– Very different
what the true effectiveness may be, it should be
considered in the context of another statistical
measure called a confidence interval that indicates
where the true result lies. The confidence interval for
CAPRISA 004 had a lower boundary of 6 percent
and an upper boundary of 60 percent.
• More information at the end
of VOICE?
– Reported
To get cadherence,
loser to the truth aboutrn ay ACASI,
p oduct’s effectiveness, more than one study is almost always
productrequired.
counts
As such, to be certain that tenofovir gel is
effective, additional data from more women was
needed.
– Drug levels,
genital swabs
There were more than 2,000 women in the two gel arms Slide
of VOICE.
Some of these
women were
also from
courtesy
Dr. Sharon
Hillier,
MTN
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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Anal intercourse is a
human behaviour.
An act of unprotected anal
intercourse is 10 to 20 times more
likely to result in HIV transmission
than an act of unprotected vaginal
intercourse.
Rectal mucosa
Slide courtesy Dr. Ian McGowan
Balls (and rectums) are fragile…
-Betty White, American television star
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
•
MTN 017
• 186 Peru, RSA, Thailand,
U.S.
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MTN-017
8 weeks
Gel
Daily
8 weeks
Gel
With Sex
8 weeks
Oral
Truvada
Gel
With Sex
Gel
Daily
Oral
Truvada
Oral
Truvada
Gel
With Sex
Gel
Daily
Slide courtesy Dr. Ian McGowan
Project Gel
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Combination Prevention
SC
±
Oral
±
Rectal
±
Vaginal
HIV Vaccine
Slide thanks to Dr. Ian McGowan, MTN
AIDS Vaccines
What you need to know about
AIDS vaccines and where we are
What you need to know about AIDS Vaccines
What is a vaccine?

An agent that stimulates an immune response to protect again disease or to modulate disease progression,
in other words, a substance that teaches the immune system how to protect itself against a virus or bacteria.

No vaccine is 100% effective. Most vaccines licensed in the US 70%-95% effective.
What types of AIDS vaccines are in development?
Preventive Vaccines
Therapeutic Vaccines
 Designed for people who are not infected with HIV
 Designed for people who are living with HIV
 Reduces risk of infection or viral load set point after
infection
 Uses the body’s immune system to control HIV in the
body
Why the interest in an AIDS vaccine?

Need for a range of HIV prevention methods (no silver bullet)

Proven prevention options have slowed HIV’s spread but thousands of people continue to get infected daily

Vaccines are one of the world’s most effective public health tools

Cost-effective (generally administered once—or a few times with boosts—for long-term or lifetime protection)

AIDS vaccines cannot cause HIV
Ongoing Phase I/II and II Preventive AIDS Vaccine Clinical Trials
2009
1
2
2010
3
4
1
2
2011
3
4
1
2
3
4
HVTN 205 US, Peru
August 2014
Phase II trial to assess safety of DNA and MVA vaccines and immune responses
of participants to see if these vaccines are helpful in fighting HIV infection.
HVTN 505 US
Expected 2013
Phase II trial to assess if DNA prime/rAd5 boost vaccine regimen significantly reduce viral load in
individuals who become infected with HIV. Results will help develop T-cell based vaccines and
information on what specific T-cell responses are most beneficial.
HVTN 078 Switzerland
Q3 2012
Phase I/II trial to assess the safety and immune response in the mucosa of the
vector vaccines NYVAC-B and the rAd5.
TaMoVac1 Tanzania, Mozambique
Ongoing
Phase I/II trial to assess the safety and immune response of DNA
priming and MVA boosting and to develop further HIV vaccine trial
capacity building in Tanzania.
HVTN 083 US
Ongoing
Phase I/II trial to assess the safety and immune response
of an adenovirus-based HIV-1 vaccine regimen.
No effective HIV Vaccines is available
today; however, more than two dozen
phase I & II trials are ongoing in 20+
countries around the world, including followon studies from recent large-scale trials.
HVTN 084
Brazil, Peru,
Switzerland, US
Phase I/II trial to assesses the safety and
immune response of two Ad5 adenoviral
vector vaccines.
Ongoing
Highlights from 2011 in AIDS vaccine research
In 2009, the RV144 Thai vaccine was the first
ever to demonstrate a modest effect of 31.2%
in preventing HIV infection. In September
2011, immune responses predictive of risk in
RV144 trial identified.
In May 2011, the Pox-Protein Public Private
Partnership or “P5” (formed by Sanofi
Pasteur, Novartis, US NIH, Gates Foundation,
the US MHRP and the HVTN) debuts,
designed to move from the RV144 Thai
prime-boost vaccine trial results to a
potentially licensable product for Thailand
and elsewhere.
In August 2011, the HVTN
505 Phase II trial of a
DNA-Ad5 combination
expands its scope to
include an investigation
of whether the
experimental vaccine
regimen prevents HIV
infection.
January
February March
April
May June
July
August September
More than two dozen phase I & II
trials are ongoing in 20+ countries
worldwide. Promising antibody
and animal studies are continuing.
Follow-on studies from
RV144 in South Africa and
Thailand are underway.
October
November December
Cure Research
Background

Invigorated by case of Tim “Berlin Patient” Brown –transplant of stem cells lacking in CCR5 receptor. Cure never
replicated.

Sterilizing cure: eliminating all HIV from the body (eradication)

Functional cure: permanent viral suppression without continuous therapy

Cure must have better outcomes than ART
Focus

HIV Latency

How does HIV persist even in patients with no detectable viral load?

How do we measure HIV latency?

How do we locate and safely activate latent HIV?

Research Sponsors; NIH - Martin Delaney Collabortory (3 grants awarded), French ANRS and some industry Merck,
Gilead, Tibotec

IAS Global Scientific Strategy Towards an HIV Cure
Approaches

Flush out and Kill: ART intensification while activating Latent HIV.

Strengthening the immune system. Therapeutic vaccines alone or with activation (Current candidates show only
modest VL reduction)

Gene therapy – for example, altering CD4 cells against HIV infection.
Now
what?
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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 gay men/MSM
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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Demo projects
SF and
Miami
Long term
toxicity
Adherence
Behavior
Right
people
Who
delivers
and where
Testing
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FDA – label change gay/MSM
FDA review
science
June 2012
Ease of
access
Global
impact
Gilead can
market
Cost reimb
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PrEP public health
response Chicago DPH
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Advocacy
mappingpathways.blogspot.com
Fenway Health, 2/22/12
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Advocacy
lifelube.blogspot.com
projectinform.org
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Advocacy
AVAC.org
Special thanks for their slides:
Cindra Feuer, AVAC
Bob Grant, iPrEx
Deirdre Grant, AVAC
Sharon Hillier, MTN
Ian McGowan, MTN
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More special thanks to YOU
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“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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Don’t be a stranger
[email protected]
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