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Topical, Oral;Daily, Intermittent;
Single, Combination agents;
What do we need AND what will work?
Patrick Ndase, Microbicide Trials Network &
Dep’t of Global Health, University of Washington
Within the research & advocacy community, there is a lot of enthusiasm & hope around the promise of ARV-based approach to HIV prevention
– Biomedical piece that will likely revolutionalize HIV prevention
THE BOLD STATEMENT
WE NEED
• Topical AND Oral ARV-based intervention– Know your HIV status = Know your options
• Daily dosing as a 1st step but Intermittent dosing based on exposure times preferred
• Single agents if efficacious & out of treatment realm desired, but the search for combination agents ought to continue
Key stakeholders’ question has been…….
• How can you explain the enthusiasm around ARV based prevention, amidst ever diminishing slots for people in desperate need of care?
– Shall funders have the much needed momentum for prevention in light of failed sustained momentum for treatment?
– Can’t the biomedical prevention approach be mismanaged?
Reminder of why we need additional prevention tools now
For every 2 people started on ART in Southern Africa, 3 become newly infected
In South Africa alone• >1500 new HIV infections are Estimated to occur daily• An approx 70,000 babies are born with HIV annually
Bottom line:We need to prevent new infections if we’re to effectively treat those who need care.
http://www.avert.org/aidssouthafrica.htm
The Face of HIV in Uganda
• 110,000 new infections every year
(> 300 new infections everyday)
• 73,000 (66%) of new infections
annually are women.
• 47% of the women living with
advanced have no access to anti-
retroviral therapy
• 52% percent access PMTCT (21%
of new infections due to MTCT)
The New York Times on Uganda
At Front Lines, AIDS War Is Falling Apart
• ~ 500,000 need treatment
• 200,000 getting treatment
• Each year approx an additional 110,000 infected
HIV slots not only limited to Uganda
• Economy Hurts Government Aid for H.I.V. Drugs, New York Times of June 30th, 2010
FORT LAUDERDALE, Fla. Nearly 1,800 have been relegated to rapidly expanding waiting lists that less than three years ago had dwindled to zero.
http://www.nytimes.com/2010/07/01/us/01aidsdrugs.html?hp
Proving the skeptics wrong
• ART roll-out in resource limited settings will never be possible– Countries now constrained with stock-outs & few slots
for new entrants
• Adherence to ART will be poor in the developing world– Some of highest reported adherence rates– Resistance a major worry due to programmatic failure
(NOT poor adherence)
Signal of willingness to access prevention services
Documented HIV Prevalence on Island is 17% [2006 Sentinel survey]
• Having sex is single most important risk factor in context of high prevalence
Up to 5hrs en-route study clinic for PrEP• Participants wake up 3:00AM to start journey• Yet with excellent retention
Topical, Oral;Daily, Intermittent;
Single, Combination agents;
What do we need AND what will work?
Is the field poised to provide all we need?
Vaccine -Prime/Boost
Thailand
Oral TDF - IDU Thailand
Oral Truvada – Heterosexual
Botswana
Oral TDF -MSM US (Ph II)
Oral Truvada - MSM (iPrEx)
Oral TDF, Truvada -
Partners PrEP
Oral Truvada - FemPrEP
Microbicide - BufferGel, PRO2000
CAPRISA 004
TDF Gel
Microbicide -PRO2000
Oral TDF & Truvada &
Tenofovir gel -VOICE
Microbicide -Dapivirine
gel & ring
2009 2010 2011+
Index Partner Treatment
HSV-2 Treatment -
Infectiousness
2015+
New Vaccine
concept(s)
Vaccine - DNA Prime/Ad5 Boost
US
TMC 278 - UK (Ph I/II)
Microbicides
PrEP
Vaccines
Treatment as PX
KEYTesting & linkage to care
plus (TLC+)
What will be lacking?
Topical / Oral VOICE efficacy & acceptability data will be critical
Daily / Intermittent No data on intermittent use & efficacyA hint from CAPRISA’s coitally dependent approach
Single / Combination agents Oral: TDF/Truvada will provide a hintNo topical combinations
The three issues here all point to efficacy;
QUESTION:But how much of an impact does efficacy have on the epidemic?
Use Microbicides/ PrEP 50%
Product 50% effective
Product 80% effective
100 Women Exposed to HIV (10% transmission risk)
50 have access
TOTAL
The Prvention Cascade – 50% Access/Adherence
Access to Microbicides/PrEP 50%
50 have no access
25 use 75 do not use
1.3 infections
0.5 infections
7.5infections
7.5infections
If 50% − 9 infections
If 80% − 8 infections
No Product − 10 infections
Use Microbicides/ PrEP 95%
Product 50% effective
Product 80% effective
100 Women Exposed to HIV (10% transmission risk)
95 have access
TOTAL
The Microbicide/PrEP Cascade – 95% Access/Adherence
Access to Microbicides/PrEP 95%
5 have no access
90 use 10 do not use
4.5 infections
1.8 infections
1infection
1infection
If 50% − 6 infections
If 80% − 3 infections
No Product – 10 infections
The prevention Cascade
Intervention effect Percent coverage Fraction of Infections prevented
80% 50% 20%
50% 95% 40%
The effectiveness of an intervention, matters but coverage matters even more
Impact of ARV-based prevention on epidemic
Modeling work (Imperial College London)
• Targeting most at-risk populations
• Extent of coverage of these populations
• Adherence/Acceptability of the interventions
An old challenge!Can we deliver on the promise?
Sources: UNAIDS, 2004; UNGASS, 2008; WHO, 2009
0% 20% 40% 60% 80% 100%
HIV testing
Antiretrovirals for PMTCT
Condom Use
Contraception for PMTCT
2004
9% 32%
9%
14%
2006/7
Male Circumcision
20% 80%
85%
10% 75%
55%
Unmet HIV Prevention Need
85%
Estimates of Coverage Unmet Need for HIV Prevention
5%
15%
15%
2008
45%
39%
25%
Thank You
The International Clinical Research Center at UW
The Microbicide Trials Network