1. Richard hayes London school of hygiene & Tropical Medicine
Adapting global and national guidelines in a large implementation science study HPTN 071 (PopART)
Richard hayes London school of hygiene & Tropical Medicine

2. acknowledgements
Sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) under Cooperative Agreements # UM1 AI068619, UM1-AI068617, and UM1-AI068613
Funded by:
The U.S. President's Emergency Plan for AIDS Relief (PEPFAR)
The International Initiative for Impact Evaluation (3ie) with support from the Bill & Melinda Gates Foundation
NIAID, the National Institute of Mental Health (NIMH), and the National Institute on Drug Abuse (NIDA) all part of the U.S. National Institutes of Health (NIH)

3. Outline of presentation
Objectives of HPTN 071 (PopART) trial
Overview of trial design
Responding to changing global and national guidelines
Transition to universal treatment
Continuing importance of study questions

4. Objectives of HPTN 071 (PopART) trial
Measure the effectiveness and cost-effectiveness of a combination prevention package
Including universal testing and treatment (UTT) and other proven HIV prevention methods
Generalised epidemic in Southern Africa – urban communities
Cluster-randomised trial
Impact on HIV incidence at population level
Implementation science: can a UTT intervention be implemented on a wide scale with high coverage?

5. ~ 2,000 random sample from each community : HIV incidence at 36 months
Trial Design
Total Population ~ 1M
~ 2,000 random sample from each community :
Population Cohort
N ~ 42,000
12 in Zambia
9 in S. Africa
Primary outcome:
HIV incidence at 36 months

6. ~ 2,000 random sample from each community : HIV incidence at 36 months
Trial Design
Total Population ~ 1M
~ 2,000 random sample from each community :
Population Cohort
N ~ 42,000
12 in Zambia
9 in S. Africa
Primary outcome:
HIV incidence at 36 months
PopART intervention package
Annual rounds of Home Based Voluntary HIV Testing by Community HIV-care Providers (CHiPs)
Health promotion, Active Referral and/or Retention in Care support by CHiPs for the following:
Voluntary Medical Male Circumcision (VMMC) for HIV negative men
Prevention of Mother to Child Transmission (PMCT) for HIV positive women
HIV treatment and care for all HIV positive individuals
Promotion of sexual health and TB services
Condom provision
ART irrespective of CD4-count or immune-status provided at the local health centre in Arm A

9. Changing guidelines for ART initiation: provisions of study protocol
Arm A: Immediate offer of ART irrespective of CD4 count
Arms B and C: ART according to current national treatment guidelines
Consent: Individuals in Arm A who are offered ART initiation outside current national treatment guidelines are asked for informed consent

10. Previous guideline changes

11. “ART should be initiated in everyone living with HIV at any CD4 cell count”

12. Trial Design
12 in Zambia
9 in S. Africa

13. Trial Design

14. Planning for expedited transition in Arms B and C
V3.0 of protocol developed to allow for transition ahead of changes in local guidelines if necessary
All required ethics approvals secured for V3.0
Transition implemented in April/May 2016 in Zambia – part of an MoH pilot preceding national roll-out – so consent no longer required
Discussions in progress with DoH and other stakeholders in SA
Study remains well-powered because projected impact limited without intensive community-based intervention

15. Study power – with and without guideline change
Over 3 years
Over years 2&3
Pessimistic
Central
Optimistic
With change
Effectiveness
36%
42%
48%
40%
47%
56%
Incidence 1%, k=0.15
Study power
84%
94%
98%
82%
93%
99%
Incidence 1.5%, k=0.2
79%
91%
97%
81%
Without change
43%
49%
57%
95%
92%
Assumes PC sample size of approximately 2,000 per community
Arm A compared with Arm C

16. Is there still equipoise?
Immediate start of ART: No longer clinical equipoise – clear evidence of benefit – reason for seeking expedited transition
But Immediate ART ≠ Test-and-Treat
Test (and retest) → Link → Start ART → Adherence/suppression
We do not know
If UTT can be delivered at population level with sustained high coverage
The impact on HIV incidence at population-level
The cost-effectiveness of this strategy
This will be key evidence to inform measures to achieve the SDGs leading to long-term elimination of HIV

17. Key questions we are trying to answer
Can a Universal Testing and Treatment (UTT) intervention be delivered on a large scale?
What uptake and coverage can be achieved by such an intervention and can this be sustained over time?
What is the impact of such an intervention on HIV incidence at population level and how does this build up over time?
What is the cost-effectiveness of the intervention?
Important to answer these questions in context of guidelines for ART initiation that will apply when study is completed!

18. The HPTN 071 Study Team, led by: PEPFAR Implementing Partners:
Dr. Richard Hayes
Dr. Sarah Fidler
Dr. Helen Ayles
Dr. Nulda Beyers
Government Agencies:
PEPFAR Implementing Partners:

19. With thanks to: All research participants and their families
The 21 research communities and their religious, traditional, secular and civil leadership structures
Volunteers in the community advisory board structures