ART for PreventionFrom Evidence to Action

Wafaa El-Sadr, MD, MPHICAP-Columbia University

The Evidence is Here!

• Ecological data• Observational studies in discordant couples• Randomized clinical trial (HPTN 052)

Number of PLWH receiving ART in low- and middle-income countries, by region, 2002–2009

UNAIDS, 2010

HIV Treatment Coverage in Low & Middle Income Countries

WHO Towards Universal Access 2010

ART for Prevention

Test

HIV Positive

Adopt safer behaviors

Enroll in Care

Treat

Maintain viralsuppression

Positive Prevention

Testing

Initiationof ART

Linkage to care

Adherence to ART

Decrease in HIV Transmission

ART for Treatment & Prevention

Test

HIV Positive

Adopt safer behaviors

Enroll in Care

Treat

Maintain viralsuppression

Positive Prevention

Testing

Initiationof ART

Linkage to care

Adherence to ART

• Decrease in HIV Transmission• Optimal Treatment Outcomes

HIV Care Continuum

HIVDiagnosis

ART

Monitoring and Retention in Care

ART eligiblePre-ART

Monitoring, Retention and Adherence Support

HIV Testing and Knowledge of HIV Status--Kenya

84% of HIV-infected adults did not know their

status.

16% knew they were positive

28% reported last

HIV-test negative

56% never tested

for HIV

KAIS, 2008

Awareness of HIV Status Among Persons with HIV and Estimates of Transmission-- US

~21% Unaware of

Infection

~75% Aware of Infection

People Living with HIV/AIDS 1,106,400

New HIV Infections Each Year: ~56,000

~54 - 70% of New

Infections

~30 - 46% of New

Infections

Marks, et al AIDS 2006

Point of Entry into HIV careICAP-Supported Programs

VCT PMTCT PICT TB/HIV Other clinic referral/unknown

January 2010-March 2011

Advances in HIV Testing• Home-based testing:

– Randomization of household members of HIV-infected patients to home-based or clinic based VCT

– Household testing versus clinic VCT: • 55.8% versus 10.9% OR: 10.4 (95% CI: 7.89-13.73; P<0.001)

• Community-based testing: Project Accept (HPTN 043) – Community-randomized study (32 communities)– Community-based plus clinic-based C&T versus clinic-based C&T– Community-based plus clinic-based:

• Mean difference in proportion tested: 40.2% (95% CI: 15.8-64.7%, P=).019• Detected four fold more HIV cases than clinic based (952 vs 265 (P=0.003))

• Self testing:– Feasibility study in Malawi – Of 260 who opted for self-test, 99.2% accurate test– 100% indicated would recommend to friends and family

Lugada et al. JAIDS, 2010Sweat et al, Lancet 2011Choko et al, CROI 2011

Expansion of Provider Initiated Testing (PIHCT)--Ethiopia

Jan-M

ar 2007

Apr-Jun 2007

Jul-Sep 2007

Oct-Dec 2

007

Jan-M

ar 2008

Apr-Jun 2008

Jul-Sep 2008

Oct-Dec 2

008

Jan-M

ar 2009

Apr-Jun 2009

Jul-Sep 2009

Oct-Dec 2

009

Jan-M

arch 2010

Apr-Jun 2010

Jul-Sep 2010

Oct-Dec 2

0100

50,000

100,000

150,000

200,000

250,000

CounseledTestedTested HIV positiveEnrolled

Quarter

Num

ber o

f pati

ents

80 health facilitiesHIV Counseled 2,077,592HIV Tested 1,762,636HIV +ve: 44,835 (2.5%)

ICAP-supported sites--Ethiopia

HIV Concordance/Discordance in Couples (DHS)

Eyawo et al. Lancet 2010

Couples Versus Individual Counseling and Testing-- Tanzania

• 1521 women attending three ANC randomized to Couples C&T versus Individual C&T

Variable Couple C&T Individual C&T

Proportion women receiving result 39% 71%

HIV positive women Receive ARV for PMTCT Infants receive ARV for PMTCT

90%55%

60%22%

Becker et al, AIDS Beh 2010

Mar-05

Mar-06

Mar-07

Mar-08

Mar-09

Mar-10

Mar-11

0

200,000

400,000

600,000

800,000

1,000,000

1,200,000

0

100

HIV Care ART

CUMULATIVE ENROLLMENT IN HIV CARE AND TREATMENT

Num

ber o

f pat

ient

s Number of clinics

561,722 on ART

1,113,543 in care

768clinics

ICAP-Supported Programs

Woman (Mother), Age: ______0 1 2 3 4 5 _____6______UAN:

Man (Father), Age: _______0 1 2 3 4 5 _ 6______UAN:

1st child, Age: _______0 1 2 3 4 5 6 7__UAN:

6th child, Age: ______ 0 1 2 3 4 5 6 7______UAN:

5th child, Age: ______0 1 2 3 4 5 6 _7______UAN:

3rd child, Age: ______0 1 2 3 4 5 6__ 7_____UAN:

2nd child, Age: ______0 1 2 3 5 4 _6 7_ _UAN:

7th child, Age: ______0 1 2 3 4 5 6_ 7_____UAN:

4th child, Age: ______0 1 2 3 4 5 6_ 7______UAN:

0 = Not counseled 4 = HIV Positive1 = Counseled not Tested 5 = Pre-ART2 = HIV-exposed infant 6 = ART3 = HIV Negative 7 = Died

Family Enrollment Form Date: ____/____/____ART Client - Unique ART No. of the Index Client:

__________________________________Pre ART Client - Pre ART Serial No (Facility card number):

___________________________Family Code Number:

_________________________________________________________

HIV Care Continuum

HIVDiagnosis

ART

Monitoring and Retention in Care

ART eligiblePre-ART

Monitoring, Retention and Adherence Support

From HIV Testing to HIV Care to ART Initiation-- Mozambique

1,506 Eligible for ART Initiation (49%)

23,430 Tested for HIV

7,005 Tested HIV positive (30%)

3,956 Enrolled HIV care < 30 days after HIV test (57%)

3,046 CD4 test <30 days after enrollment (77%)

317 Adherent to ART for 6 months (83%)

3,049 (43%) not enrolled in HIV care

910 (23%) No CD4 test drawn

1,035 (69%) did not initiate ART

65 (14%) LTFU after ART

471 Initiated ART < 90 days after CD4 test (31%)

Micek et al JAIDS 2009

• 62.6% newly diagnosed patients linked to care

• Highest % linkage in STI tested (84.1%)

• Lowest % linkage in VCT (53.5%)

Kranzer Plos Med 2010

HIV Care Cascadeby Testing Site

Eggers et al, CROI 2007

Median CD4 Count at Enrollment into Care, by Point of Referral

VCTPICT

PMTCT

TB/HIV

Other c

linic r

eferra

l/unkn

own

0100200300400500600700

Point of referral into HIV care

Medi

an C

D4 co

unt (

cells

/uL)

at en

rollm

ent

into

care

ICAP-Supported Programs

Median CD4 count at enrollment into care, by enrollment year

2005 2006 2007 2008 2009 2010 20110

100

200

300

400

500

600

OverallKenyaMozambiqueRwandaTanzania

Year of enrollment into care

Medi

an C

D4 c

ount

(Cel

ls/u

L) a

t enr

ollm

ent i

nto

care

242 cells/ul

306 cells/uL

ICAP-Supported Programs

HIV Care Continuum

HIVDiagnosis

ART

Monitoring and Retention in Care

ART eligiblePre-ART

Monitoring, Retention and Adherence Support

Retention in ART ProgramsMeta-analysis SSA

Fox and Rosen, Trop Med Int Health 2010

36 cohorts226,307 patientsAll losses except transfers

Retention:• 6 months: 86.1%• 12 months: 80.2%• 24 months: 76.8%• 36 months: 72.3%

InterventionsIntervention Outcome

POC CD4 at HIV Test Linkage to careART initiation

Case Manager Linkage to care

Adherence support activities(counseling, home visits, treatment preparation, supportive supervision by RN

Retention and ART adherence

Cash transfer (transport) Retention

Free cotrimoxazole Retention of pre-ART patients

Food package Visit adherence

Peer educators Retention (not adherence)

SMS messaging Adherence

Faal et al IAS 2010Jani et al IAS 2010 Gardner et al JAMA 2005 Etienne et al. Trop Med Int Health 2010

Emenyonu CROI 2010Kohler et al CROI 2011Ivers et al. AIDS Res Therapy 2010Chang et al, Plos One June 2010

ART for Prevention: A Multi-Component Strategy

• Expanded testing• Linkage to care• Initiation of ART• Adherence support • Positive prevention

Testing

Linkage

Antiretroviral Treatment

Adherence

Positive Prevention

• Community Mobilization• Policies and Guidelines• Buy-in by PLWH

Plus

Time for Action

HIV Prevention Trial (HPTN 052) Releases New FindingsEarly initiation of ART leads to 96% reduction in HIV transmissionaccording to study conducted by HIV Prevention Trials Network 

PIVOTAL STUDY FINDS THAT HIV MEDICATIONS ARE HIGHLY EFFECTIVE ASPROPHYLAXIS AGAINST HIV INFECTION IN MEN AND WOMEN IN AFRICA

Granich et al Lancet 2009; 373:48-57

ART for Prevention

• 95% reduction in new HIV cases in 10 years

• HIV Incidence reduced from

15-20,000 to 1000 per million

• Prevalence decreases to less than 1% by 2050

Granich et al, Lancet 2009

• Annual testing by all >15 year old individuals• All HIV+ individuals started on ART immediately • 99% decrease in infectiousness• High adherence with ART• Low failure with first line ART

El-Sadr, Coburn, Blower

Populations Demographics and Couple Serostatus

Change in HIV Incidence with Increasing ART Coverage in Discordant Couples

El-Sadr, Coburn, Blower

Treatment Coverage and Infections Prevented

Conclusions-1

• Evidence accumulating on the value of ART for prevention of HIV transmission

• Several challenges and opportunities impede/enable the potential of ART for prevention (and for treatment)– Expansion of HIV testing – Identification of individuals earlier in HIV disease– Optimization of HIV care cascade

(from testing to linkage to ART initiation to retention and adherence)

Seek, Link, Treat, Retain and Support

Conclusions-2

• Implementation and scale-up need to be guided by evidence, prioritization, adaptation, innovation, monitoring and evaluation

• Need for continued research to:– Determine the feasibility and effectiveness of ART as prevention at a

population level– Examine the effect(s) of combined interventions– Identify interventions to enable/maximizing every step of the HIV care

cascade – Conduct modeling to guide prioritization and action at country levels

Thank you