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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• Tekst• Tekst
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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