Topical, Oral; Daily, Intermittent; Single, Combination agents;

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

THE BOLD STATEMENT 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

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?

HSV-2 Treatment - Infectiousness Index Partner Treatment Microbicide - BufferGel, PRO2000 CAPRISA 004 TDF Gel Microbicide - Dapivirine gel & ring Oral TDF & Truvada & Tenofovir gel - VOICE Microbicide - PRO2000 Oral TDF -MSM US (Ph II) Oral Truvada - MSM (iPrEx) Oral TDF, Truvada - Partners PrEP Oral Truvada – Heterosexual Botswana Oral Truvada - FemPrEP Oral TDF - IDU Thailand Is the field poised to provide all we need? KEY Testing & linkage to care plus (TLC+) Treatment as PX Vaccines Microbicides Vaccine - Prime/Boost Thailand Vaccine - DNA Prime/Ad5 Boost US New Vaccine concept(s) PrEP TMC 278 - UK (Ph I/II) 2011+ 2010 2015+ 2009

What will be lacking? The three issues here all point to efficacy; QUESTION: But how much of an impact does efficacy have on the epidemic?

The Prvention Cascade – 50% Access/Adherence 100 Women Exposed to HIV (10% transmission risk) Access to Microbicides/ PrEP 50% 50 have access 50 have no access TOTAL 25 use Use Microbicides/ PrEP50% 75 do not use No Product − 10 infections 1.3 infections 7.5 infections If 50% − 9 infections Product50%effective 0.5 infections 7.5 infections Product80%effective If 80% − 8 infections

The Microbicide/PrEP Cascade – 95% Access/Adherence 100 Women Exposed to HIV (10% transmission risk) Access to Microbicides/ PrEP 95% 95 have access 5 have no access TOTAL 90 use Use Microbicides/ PrEP95% 10 do not use No Product – 10 infections If 50% − 6 infections 4.5 infections 1 infection Product50%effective 1.8 infections 1 infection Product80%effective If 80% − 3 infections

The prevention Cascade 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? Estimates of Coverage Unmet Need for HIV Prevention HIV testing 5% 20% 39% 80% Condom Use 15% 85% 9% Male Circumcision 10% 75% 25% Antiretrovirals for PMTCT 9% 32% 45% 55% Contraception for PMTCT 85% 14% 15% 0% 40% 60% 80% 100% 20% 2006/7 2004 Unmet HIV Prevention Need 2008 Sources: UNAIDS, 2004; UNGASS, 2008; WHO, 2009

Thank You The Microbicide Trials Network The International Clinical Research Center at UW

Topical, Oral; Daily, Intermittent; Single, Combination agents;