ART for prevention: background

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Transcript ART for prevention: background

Treatment as prevention: a new paradigm
for HIV control?
Richard Hayes
Treatment as prevention
• Background and rationale
• Design of PopART/HPTN071 trial
• Other planned trials
ART for prevention: background
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HIV incidence continues to be unacceptably high in many
countries in Africa
Lack of proven effective HIV prevention strategies
Unless incidence can be reduced dramatically it will
become increasingly difficult over time to sustain effective
ART services
Lancet 2009 373: 48-57
ART for prevention: background
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HIV incidence continues to be unacceptably high in many
countries in Africa
Lack of proven effective HIV prevention strategies
Unless incidence can be reduced dramatically it will
become increasingly difficult over time to sustain effective
ART services
Risk of HIV transmission closely correlated with HIV viral
load and ART can be used to reduce HIV viral load and
hence infectivity
Rakai Study of viral load and HIV
transmission
Quinn et al, NEJM 2000
Evidence from HPTN 052
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1763 HIV-discordant couples in 9 countries, CD4=250-550
Randomized to immediate or deferred treatment
Stopped for efficacy
39 HIV-ve partners were infected of which 29 were linked
virologically to the infected partner
Of these 29 only 1 was in the immediate treatment group
HR = 0.04 (95% CI: 0.01–0.27)
Also significant reduction in morbidity endpoints in treated
individuals – HR for serious clinical endpoints = 0.59 (95%
CI: 0.40-0.88)
ART for prevention: background
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HIV incidence continues to be unacceptably high in many
countries in Africa
Lack of proven effective HIV prevention strategies
Unless incidence can be reduced dramatically it will
become increasingly difficult over time to sustain effective
ART services
Risk of HIV transmission closely correlated with HIV viral
load and ART can be used to reduce HIV viral load and
hence infectivity
Current guidelines limit ART to those with late-stage HIV
infection (CD4<200 or CD4<350) but most transmission
occurs before that
Universal test and treat intervention
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Promote universal HIV voluntary counselling and testing at
regular intervals
All those diagnosed HIV positive are started on ART
immediately
Model shows immediate increase in numbers needing
treatment but in medium-term, HIV incidence and
prevalence are reduced dramatically
In long-term, numbers needing ART are reduced.
Why is a trial needed?
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Not known whether a UTT intervention can be delivered
with high uptake and acceptability
Many uncertainties in model parameters
Population-level impact of (feasible) intervention package is
not known
Many potential adverse effects, such as toxicity, drug
resistance, sexual risk disinhibition, HIV-related stigma,
overload of health services
A rigorously designed trial can measure the costs and
benefits of this strategy and provide reliable evidence on
cost-effectiveness for health policy makers
HPTN 071 = PopART
Population effect of universal testing and
immediate ART therapy to Reduce HIV
Transmission
The PopART intervention package
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Universal voluntary HIV testing delivered through a houseto-house campaign
Male circumcision offered to men who test HIV-negative
Immediate ART offered to all who test HIV-positive
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Counselling and condom provision
Strengthening of PMTCT services
Syndromic STI treatment at clinic
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CHiPs team (Community HIV Providers) to deliver testing,
counselling, linkage to care and treatment support
Additional benefits of intervention –
individual and public health
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Reduction of morbidity and mortality in those receiving ART
through earlier onset of treatment
Simplification of ART delivery and monitoring
Reduction of adverse effects of treatment
Reduction of clinic burden of TB and other illnesses
(Potential) elimination of mother to child HIV transmission
(Eventual) cost savings
Normalisation of HIV and reduction in HIV-related stigma
Reduces need for specially targeted interventions
Design of trial
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24 clusters (15 in Zambia + 9 in S Africa)
Cluster = community served by a health facility
Variable population size but averages 50-60k
Clusters matched into triplets by HIV prevalence: 5 triplets
in Zambia, 3 in S Africa
Clusters randomly allocated to 3 study arms within each
matched triplet
Restricted randomisation used to ensure balance on ART
uptake, population size and HIV prevalence
Location of study clusters
Study arms
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Arm A (8 clusters): Full PopART intervention including
immediate ART irrespective of CD4 count
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Arm B (8 clusters): Full PopART intervention except that
ART is initiated according to current national guidelines
(CD4 < 350 or WHO stage 3/4)
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Arm C (8 clusters): Standard of care
Evaluation surveys
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Population cohort (All 3 arms)
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2,500 adults aged 18-44 sampled randomly from general
population of each cluster (1 adult per household)
Total size of cohort = 2,500 x 24 = 60,000
Followed up after 1 year and 2 years of intervention
Population cross-sectional survey (All 3 arms)
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500 adults aged 18-44 sampled randomly from general
population of each cluster (all adults in selected households)
Total size of survey = 500 x 24 = 12,000
At final follow-up after 2 years of intervention
Evaluation surveys
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Clinic cohort (All 3 arms)
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Sample of 300 HIV+ve patients presenting at clinic to
register for HIV treatment and care
Total size of cohort = 300 x 24 = 7,200
Followed up for 2 years
Primary outcome
Population cohort
• HIV incidence over 2 years
• Will also look at impact during first year and second year of
follow-up
Secondary outcomes
Population cohort
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HSV-2 incidence (marker of risk behaviour)
Population cohort and Population cross-sectional survey
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Sexual risk behaviour and HIV-related stigma
Community HIV viral load, CD4 count, drug resistance
Uptake of services
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HIV-free infant survival
TB prevalence
Secondary outcomes
Clinic cohort
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HIV disease progression, CD4 count, morbid events
ART adherence and viral suppression
Drug resistance
Clinic and CHiPs records
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Uptake of services
TB case notification, clinic burden by cause
Model projections of impact
Targets and projected impact
Sample size for Arm A or B vs C
Funding of PopART/HPTN071
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OGAC (PEPFAR)
Bill & Melinda Gates Foundation
NIH
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PopART is one of 3 trials of combination HIV prevention
supported by OGAC
2 other trials in Botswana (Harvard) and Tanzania (JHU)
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Other planned trials (1)
Iringa, Tanzania (2 arms)
• Arm A: Expanded testing/linkage to care, ART at CD4<350, IEC,
male circumcision, conditional cash transfers, targeted outreach
• Arm B: Standard of care
• 24 clusters (12 vs 12)
• Cohort of 500/cluster, total 12,000, 24m follow-up
Botswana (2 arms)
• Arm A: Expanded testing/linkage to care, ART at CD4<350 OR
VL>10,000, male circumcision
• Arm B: Standard of care
• 20 clusters (10 vs 10)
• Cohort of 500/cluster, total 10,000, 36-48m follow-up
Other planned trials (2)
KwaZulu Natal, S Africa (2 arms) – TasP trial
• Arm A: Expanded testing, male circumcision, immediate ART,
IEC, STI treatment etc.
• Arm B: As above but ART at CD4<350
• 32 clusters (16 vs 16)
• 1,250/cluster, total 40,000, 24m follow-up (total population)
• Funding currently available for initial feasibility study in 4 of the
32 clusters
The HPTN 071 team
LSHTM
Richard Hayes
Debby Watson-Jones
Kalpana Sabapathy
Sian Floyd
Lucy Bradshaw
Zambart
Helen Ayles
Virginia Bond
Nathaniel Chisinga
Ab Schaap
Imperial College
Sarah Fidler
Christophe Fraser
Peter Smith
Desmond Tutu TB Centre
Nulda Beyers
Peter Bock
Lyn Horne
The HPTN 071 research team
HPTN/FHI360
Sten Vermund
Ayana Moore
Sam Griffith
Rhonda White
HPTN Network Lab
Sue Eshleman
Estelle Piwowar-Manning
DAIDS
David Burns
Peter Kim
SCHARP
Deborah Donnell
Lynda Emel