Prevention Today: What’s the Right Mix? Scientific

OverviewCatherine Hankins BA MD MSc FRCPC

Deputy Director, ScienceAmsterdam Institute for Global Health and

DevelopmentHonorary Professor

London School of Hygiene and Tropical MedicineAIDS 2012: Turning the Tide Together

19th International AIDS ConferenceWashington, DC, USA

Prevention Today: What’s the Right Mix? Scientific

OverviewInvestment choicesCombination prevention of sexual

transmissionOverview of trial results: what

works, what doesn’t, what’s nextKnow your epidemic/know your

response

AIDS investment framework

SYNERGIES WITH DEVELOPMENT SECTORSSocial protection; Education; Legal Reform; Gender equality; Poverty reduction; Gender-based violence; Health systems (incl. treatment of STIs, blood safety); Community systems; Employer practices.

CRITICAL ENABLERS

Social enablers• Political commitment &

advocacy• Laws, policies &

practices• Community

mobilization• Stigma reduction• Mass media• Local responses, to

change risk environment

Programme enablers• Community-centered

design & delivery• Programme

communication• Management & incentives• Production & distribution• Research & innovation

Care & treatment

Male circumcision

Keeping people alive

BASIC PROGRAMME ACTIVITIES

Keypopulations

Children &mothers

Condoms

OBJECTIVES

Stopping new infections

Behaviourchange

Combination Prevention: Basic Attributes• Tailored to national and local needs and contexts • Combines biomedical, behavioural and structural

elements—to reduce both immediate risks and underlying vulnerabilities

• Fully engages affected communities, promoting human rights and gender equality

• Operates synergistically on multiple levels—individual, family and society

• Invests in decentralized and community responses and enhances coordination and management

• Flexible—adapts to changing epidemic patterns and can rapidly deploy innovations

Adapted from UNAIDS 2010

Opportunities for Preventing Sexually Transmitted HIV Infection

Topical microbicides,

oral PrEP, Vaccine,

Condoms

Vaccine, PEP

Behavioural, structural

Male circumcision, Vaccine, Condoms

Treatment of HIV, reduced infectivity

Cohen et al. J. Clin. Invest. 118:4, 2008

Years Hours 72h – 28d Years

Unexposed Exposed(precoital/coital)

Exposed(postcoital)

Infected

Biomedical and Behavioural Prevention

Grant NEJM 2010Baeton NEJM 2012Thigpen NEJM 2012

Behavioural change• Abstinence• Be faithful

Male and Female CondomsMale condom effectiveness

• Meta-analyses: Greater than 90% when used correctly and consistently (Condoms for HIV prevention in developing countries: a review of the scientific literature. UNAIDS 2003)

• Cochrane Review: always vs. never: 80% reduction in incidence

Female condoms: (Peters et al 2010)• price monopolies

• 25 times price of male condom• WHO ambivalence re washing and reuse• lack of active promotion by UNAIDS: low demand• stock-outs• underproduction with no economies of scale• good acceptability with frustrated demand

Scientific Evidence: Male Circumcision Reduces HIV Risk in

men

Risk ratio0.2 0.3 0.40.5 1 1.5

Risk ratio (95% CI) 0.42 (0.34,0.54) Observational studies

0.41 (0.24,0.69) South Africa 0.41 (0.24,0.70) Kenya 0.43 (0.24,0.75) Uganda

0.42 (0.31,0.57) p<0.0001

Overall (95% CI)

Weiss et al AIDS 2008: 22: 567-574Favours male circumcision

Favours lack of circumcision

Gray, Kigozi, Kong et al AIDS 2012; 26:609-15

Effect Persists 5 years Post-trial Follow-up

Kisumu, Kenya 66% reduction over 4.5 years. Bailey et alOrange Farm, South Africa HIV incidence 65% lower among circumcised men. Lissouba et al BMC Inf Dis 2011

Number and % Infections Averted to 2025 by Scale-up to 80% Coverage by 2015

Hankins, Forsythe, Njeuhmeli PLoS Med 2011

On near horizon: Devices for adults

Shang Ring

AlisklampPrePE

X

Barone et al JAIDS 2011 (Kenya)Musau et al J Urol 2011 (Kenya)Bitega et al JAIDS 2012 (Rwanda)

Antiretroviral Drugs for HIV PreventionAntiretroviral therapy for HIV+ persons

Reduce onward transmission Prevent vertical transmission (through

maternal treatment) Prevent horizontal transmission:

T4P: treatment for prevention before CD4+ cells reach 350/uL (HPTN 052 – 96%)

Antiretroviral prevention for HIV- persons Reduce HIV acquisition

Prevent vertical transmission (infant during breastfeeding

Pre-exposure prophylaxis to prevent horizontal transmission (MF; MM; FM)

96% Results of the HPTN052 trial announced on 12 May 2011 show that if an HIV-positive person adheres to an effective antiretroviral therapy regimen, the risk of transmitting the virus to their uninfected sexual partner can be reduced by 96%

Treatment for prevention is a game changer.Michel SidibeExecutive Director of UNAIDS

Starting at CD4 350-550 versus

CD4 less than 250

CD4 Cell Count at ART Initiation

CountryYear of

publication

CD4 count(cells/mm3)

Type of estimate n Source

ART-LINC (multiregion) 2008 114 (61-181) Median 29,175 AIDS,12; 22: 2291–2302

Jamaica 2010 186 Mean 165 Clark et al., West Indian Medical Journal, 59, 439

Mozambique 2010 138 - 165 Median 134 Jani et al., unpublished data

Uganda (Taso cohort) 2011 142 (70-206) Median (IQR) 23,315 Mills et al. AIDS 2011, 25

Togo 2010 134 Mean 5106 Mouhari-Toure et al., Med Mal Infect

Treat Asia Cohort 2010 112 (37- 209) Median (IQR) 4056 Zhou et al, BMC Infect Dis. 2010; 10: 361.

Ethiopia 2010 114 ± 71 Mean (sd) 1166 Huruy et al., AIDS Res Ther. 2010; 7: 46

South Africa 2010 81 (36–132) Median (IQR) 538 Bassett et al., AIDS 2010, 24 (suppl 1):S37–S44

ICAP: Ethiopia, Kenya, Nigeria, Lesotho, Mozambique,

Rwanda, South Africa,

Tanzania

2011 136 Median 121,506 Nash et al. AIDS 2011; 25:1523-33

Adapted from Vitoria et al, ICASA 2011

Tanser et al CROI 2012

Patients on treatment:Individual, geo-located adult patients actively on treatment in June (2004-2011)

HIV-infected:Individual, geo-located, HIV-positive adults identified through population-based HIV surveillance data (2004-2011)

Antiretroviral treatment coverage 2004-2011

<10% 10-20% 20-30% 30-40% >40%000

001

002

Proportion of all HIV-infected people receiving ART

Adju

sted

haz

ard

ratio

p=0.002

p<0.001p=0.016

p=0.590

Tanser et al CROI 2012

Adjusted HIV Acquisition Hazard by ART Coverage Category: Hlabisa,

South Africa

Adjusted for age, sex, community-level HIV prevalence, urban vs. rural, marital status, >1 partner in last 12 months, and household wealth index

Tenofovir (TDF) Tenofovir/emtricitabine TDF/FTC

Pre-exposure prophylaxis strategies

Topical PrEP: 1% tenofovir gel

Injectable PrEP: subcutaneous or intramuscular (Phase 1 trials))

iPrEx Partners

PrEP TDF2

CAPRISA 004

ASPIRE and IPM trialsIntermittent PrEP

trials

Pre-exposure Prophylaxis for Women

as of July 2012Trial Country

1% Tenofovir vaginal gel

Oral Tenofovir daily tablets

Oral Tenofovir/FTC daily tablets

CAPRISA 004

South Africa ✔ - -

VOICE gel Uganda, South Africa, Zimbabwe

X - -

FACTS 001 South Africa ? - -Fem PrEP Ken, SA,

Tanz- - X

VOICE oral Uga, SA, Zim

- X ?

Partners PrEP

Kenya, Uganda

- ✔ ✔

TDF-2 Botswana - - ✔

Systemic Versus Topical Administration

in Women

Fem-PrEP: Adherence measurements

Van Damme CROI 2012, LB32 More info NEJM 2012

CAPRISA 004: Adherence is critical to efficacy against HIV

• High (>80% gel adherence): n=336 (38%)

54% efficacy

• Intermediate (50-80% adhere): n=181 (20%)

38% efficacy

• Low (<50% gel adherence): n=367 (42%)

28% efficacyAbdool Karim et al, Science 2010

iPrEx: Adherence is Critical to Efficacy

Efficacy by as-treated analysis(data as of Nov 21, 2011)

High (≥ 90% adherence; 49% of visits)

68% efficacy

Intermediate (50-90% adherence; 33% of visits)

34% efficacy

Low (< 50% adherence;18% of visits)

16% efficacy 9% of seroconverters had detectable drug at first

HIV+ visit versus 51% of nonseroconvertersGrant et al, NEJM 2010

CD4 binding site

Technological advances in virology

From weeks of waiting for results to point of care testing

From discovering HIV in 1983 to high throughput screening for neutralizing antibodies

Population-based studies of combination prevention

Titel

Population-based studies of combination prevention

Courtesy El-Sadr. CROI 2012

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Clinical Trial Evidence: Prevention of Sexual HIV

Transmission

75% (55; 87)

62% (22; 83)

The choice of the mix of prevention interventions is not always tailored to the structure of the epidemic

Key pops

Know your epidemic/know your response

Hankins and De Zalduondo AIDS 2010

EVIDENCE

CONTEXT

EPI REVIEW

RESPONSE REVIEW

RESOURCE REVIEW

CONSULTATION & REPROGRAMMING

With thanks to:

• Helen Weiss• Myron Cohen• Kiwango Agot• Jared Beaton• Frank Tanser• Salim Abdool Karim• Wafaa El-Sadr• Marco Vitoria• Lut Van Damme• Connnie Celum• Barbara de Zalduondo• Eleanour Gouws

• Carl Dieffenbach• Quarraisha Abdool

Karim• Dawn Smith• Lynn Paxton• Bob Grant• Kevin O’Reilly• Emmanuel Njeuhmeli• Eddy Beck• ….and other

colleagues