Use of Antivirals in Prevention: Current Challenges and Controversies:

Treatment for PreventionIAS 2011

Nancy Padian

Senior technical consultant OGAC/PEPFARUC Berkeley

Outline

• Review of the evidence• Implementation Science Challenges–Burden on health systems– Testing and linkages to care– Eligibility–Adherence–Prioritizing distribution

Evidence for treatment for prevention

Ecological Studies and ART

• Population Level Benefit• San Francisco (PloS One, 2010)• British Columbia (Lancet, 2010)

• Ambiguous Benefit?• Amsterdam • France• Australia

(Cohen et al, Current Opinion HIV 2011)

Modeling Population-Level ART Effects Cohen and Gay, CID 2010

1st author (yr) Key assumptions Results

Blower (2000) Steady risk behavior levels; low resistance rate; 50% - 90% ART coverage

substantial ↓in HIV incidence

Lima (2008) 75% - 100% ART coverage when CD4 < 200; stable adherence

37% - 62% ↓ in HIV incidence

Granich (2009) Universal annual HIV testing & immediate treatment

African HIV epidemic could be ended

Law (2001) 2X-10X ↓ in infectiousness; 40% - 70% ↑ in unsafe sex

Behavioral disinhibition could limit preventive benefit

Fraser (2004) Viral load suppression on ART limits transmission; 66% ↑ in risk behavior

Behavioral disinhibition could limit preventive benefit

Wilson (2008) Effective ART reduces viral load to < 10 copies / mL; decreased condom use

Behavioral disinhibition could limit preventive benefit

Baggaley (2006) Treatment of all w/ AIDS & pre-AIDS; decreased risk-taking

Only small number of infections averted

HPTN 052

1763 discordant heterosexual couples(9 countries, 13 sites)

Immediate ART350-550cells/uL

Deferred ART CD4 <250AZT+3TC+EFV

Endpoints: i) HIV transmission to partners ii) OIs and clinical events iii) ART toxicity

Randomization

HPTN 052 Prevention Results 39 total infections, 35 in the delayed arm (p<.0001)– 28 linked infections (by 3 independent methods) • 27 delayed arm• 1 immediate arm

o 17 of 27 infections in delayed arm occurred when the index participants’ CD4 was >350

– 7 unlinked infections• 4 delayed arm (all now proven unlinked)• 3 immediate arm (all now proven unlinked)

– 4 infections still being analyzed (all in the delayed arm)

– The details of 1/27 transmissions are being evaluated

p<0.001

Effect of ART at Population Level

• Depends on:–durable and reliable HIV suppression–preventing transmitted resistance–dealing with acute HIV infection–numerous implementation issues

Implementation Science Challenges

Added Burden to Health System

• Human Resources– Task shifting• Increased training

• Structural Resources• Centralized and Decentralized care• Increased Commodities– (e.g. test kits, drugs)

HIV testing and linkages to care

• Consider supply side interventions – PBF/P4P– CCT

• Develop service delivery models that:– Optimize testing uptake and increase demand– Optimize linkages to care and treatment– Protect patient rights and confidentiality– Examples

• Demand-side incentives• Home-based, door-to-door testing• Non-medical venues (hair salons, markets)

Knowledge of HIV Status among PLWH – Kenya

84% of HIV-infected adults did not know their status.

16% knew they were positive

28% reported last HIV-test

negative

56% nevertested

for HIV

KAIS, 2008

Gardner et al, CID. 2010: “ We estimate that only 19% of HIV-infected individuals in the United States have an undetectable HIV load.”

Barriers to Introducing & Scaling up Core Interventions for IDUs

• NSP– Police harassment – Administrative and pretrial detention without due process– Type of syringes distributed not always acceptable– High threshold policies and programmatic requirements constrain

program and coverage

• Test– Stigma and discrimination – Testing in government-run facilities– Lack of confidentiality of test results– No or limited/inaccessible services available – Operational policies limit accessibility of testing (e.g. Only

phlebotomists can administer test, limited use of rapid testing technologies, delay in receipt of positive results)

Barriers to Introducing & Scaling Up Core Interventions for IDUs

• Treat– ART

• Eligibility criteria excludes active IDUs from ART• MAT often necessary before approval for ART initiation• Stock outs of ART • MAT not widely available

– MAT• Register with authorities before eligible for services • Police harassment • Information shared between health and law enforcement• Lose rights to gainful employment, child custody• High threshold policies and programmatic requirements

constrain program and coverage • Stock outs

Eligibility• Right people, right drug concentration,

right agent, right time• Requires high uptake of frequent testing• How to identify most contagious people

early– Early, acute infection–Challenges linking asymptomatic people to

care• Need for acute infection incidence assay

Powers et al, Lancet 2011. Overall 38.4% of HIV transmissions in Lilongwe attributed to sexual contact with individuals with early infection

Adherence• Innovative strategies for real time monitoring• Less adherent-dependent doses• Innovative delivery systems; long-acting, slow

release• Rings• Implants• Patches

• Better tolerated products

A cornerstone for combination prevention

• Behavior change– Adherence– Risk compensation• condoms• number of partners

• Links to: circumcision, PMTCT, PrEP, care, structural programs (especially for young women)

How to Prioritize Distribution

• Pregnant women

• Discordant couples

• Stigmatized and marginalized high risk groups– (e.g. FSW, IDU, HIV+)

• Children

Challenge is how to ensure equity when treatment is not yet available to all who need it

Many Thanks!!

Mike CohenWafaa El-Sadr

Rich Needles