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