Women and ARV-based Prevention:Challenges and Opportunities

Tim Mastro, MD, DTM&H

AIDS 2014Melbourne, Australia24 July 2014

Women and Risk for HIV Infection

2

• Women at risk due to complex mix of biological, behavioral, structural, cultural and social factors• Varying risk

• Young women in Africa at particular risk• HIV incidence: 4% to 9% per year in recent

studies, despite best available HIV prevention • Risk perception often low, despite high rates of

HIV

Age Group (Years)

HIV Prevalence(N=1237)

≤16 10.6%

17-18 21.3%

19-20 33.0%

21-22 44.3%

23-24 51.1%

HIV prevalence in pregnant women in

rural Vulindlela, South Africa

Structural Interventions

Medication assisted therapy for people

who use drugs

Clean injection equipment for people who inject drugs

PMTCT

ARV PrEP

Behavioral Interventions

HIV Testing and Counselling

Male & femalecondoms

Blood Supply Screening

Male circumcision

ART – Treatment asPrevention

Treatmentof STIs

COMBINATION HIV

Prevention

Approaches to Reducing HIV Transmission

Exposure to HIV

INFECTEDPARTNER

Reduce infectiousness Reduce susceptibility

Reduce exposure

HIV+ HIV-

EXPOSED PARTNER

HIV Suppression Stops Transmission

6

96%HPTN 052: If an HIV-infected person adheres to ART, the risk of transmitting the virus is reduced by 96%

UNAIDS 2011 AIDS at 30SMARTER , FASTER , BETTER CAMPAIGN

“HPTN 052 is a game changer”

Michel Sidibe,Executive Director of UNAIDS

ART Coverage and HIV Incidence, KwaZulu Natal, South Africa

7

• Africa Centre, Univ of KwaZulu Natal• Africa’s largest population-based cohort study;

>16,000 HIV-negative people followed, 2004-11• HIV incidence decline associated with increased

ART coverage• Communities with 30-40% ART coverage had 38%

lower HIV incidence than communities with <10% ART coverage

Tanser F, Science, Feb 2013

HIV prevention, care and treatment cascade – major gaps in operational guidance

Viral suppression

People aware of HIV status

on ART

All peopleReachedby prevention in the health sector

Enrolled in HIV care

HIV+

HIV-

Prevention targeting

HTC demandcreation

Referral Retained Retained

Prevention opportunities for negatives

Prevention opportunities for PLWHIV, care and treatment for PLWHIV

HIV+ HIV+ HIV+

HIV-

HIV-

Effectiveness in HIV Prevention Trials

9 Efficacy

Study Effect size (CI)

TDF/FTC oral PrEP(iPrEx, 2010)

44% (15, 63)

TDF oral PrEP(Partners PrEP, 2011)

62% (34, 78)

0% 20 40 60 80 100%

63% (22, 83)TDF/FTC oral PrEP (TDF2, CDC, 2011)

Medical male circumcision (x3)(Orange Farm, 2005; Rakai, Kisumu, 2007)

57% (42, 68)

Prime-Boost vaccine(Thai RV144, 2009)

31% (1, 51)

1% tenofovir gel(CAPRISA 004, 2010)

39% (6, 60)

TDF/FTC oral PrEP(Partners PrEP, 2011)

Immediate ART for HIV-positive partners(HPTN 052, 2011)

73% (49, 85)

96% (82, 99)

TDF oral PrEP (CDC, IDU, 2013)

49% (10, 72)

10

Challenges

Effectiveness in HIV Prevention Trials

11 Efficacy

Study Effect size (CI)

TDF/FTC oral PrEP(iPrEx, 2010)

44% (15, 63)

TDF oral PrEP(Partners PrEP, 2011)

0 - 62% (0, 78)

0% 20 40 60 80 100%

63% (22, 83)TDF/FTC oral PrEP (TDF2, CDC, 2011)

Medical male circumcision (x3)(Orange Farm, 2005; Rakai, Kisumu, 2007)

57% (42, 68)

Prime-Boost vaccine(Thai RV144, 2009)

31% (1, 51)

1% tenofovir gel(CAPRISA 004, 2010)

- 39% ( 60)

TDF/FTC oral PrEP(Partners PrEP, 2011)

Immediate ART for HIV-positive partners(HPTN 052, 2011)

0 - 73% (0, 85)

96% (82, 99)

(VOICE, 2011)

(VOICE, 2011)

(FEM-PrEP, 2011; VOICE, 2013)

0 0,

TDF oral PrEP(CDC, IDU, 2013)

49% (10, 72)

0 20 40 60 80 100-60

-40

-20

0

20

40

60

80

Adherence by drug levels

Eff

ecti

ven

ess

(%)

Pearson correlation = 0.86, p=0.003

Effectiveness by adherence

Source: Salim S. Abdool Karim, personal communication

Summary of PrEP Trials for Women

13

• Tenofovir gel safe & effective in CAPRISA-004 (BAT-24 dosing). But, not effective in VOICE (daily dosing)• FACT 001 (BAT-24) ongoing, results in 2015

• TDF/FTC (daily) effective and well tolerated:– For hetero men & women in CDC TDF2 and Partners

PrEP (also showed TDF effective)– But, not effective for women in FEM-PrEP and

VOICE (low adherence) • Demonstration programs ongoing, or planned

14

Opportunities

Long-acting ARV Products

15

• Dapivirine (NNRTI) vaginal ring; monthly• ASPIRE (MTN 020) & IPM RING Study ongoing• Expect results in 2015

• Vaginal rings – multipurpose prevention• Injectable, long-acting agents – 1-3 monthly

• TMC278 LA (rilpivirine, NNRTI) • GSK744LA (integrase inhibitor)

Issues for ARVs for Prevention

16

• Who will use PrEP?• For what phase(s) of life?• For how long?• Who will pay?• Intermittent dosing?• Adherence• Service delivery• Reproductive health needs• Many, many more………..