Open Access Study protocol

HPTN 071 (PopART): Rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment – a study protocol for a cluster randomised trial

Richard Hayes1, Helen Ayles23, Nulda Beyers4, Kalpana Sabapathy1*, Sian Floyd1, Kwame Shanaube3, Peter Bock4, Sam Griffith5, Ayana Moore5, Deborah Watson-Jones2, Christophe Fraser6, Sten H Vermund7, Sarah Fidler8 and The HPTN 071 (PopART) Study Team

Author Affiliations

1 Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

2 Department of Clinical Research, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

3 Zambia AIDS Related TB Project, University of Zambia, Rideway Campus, Nationalist Road, Lusaka, Zambia

4 Desmond Tutu TB Centre, Stellenbosch University, Francie van Zijl Avenue, Clinical Building, K Floor, Romm 0065, Tygerberg Campus, Western Cape 7505, South Africa

5 FHI360, Science Facilitation Department, 2224 E NC Hwy 54, Durham, NC 27713, USA

6 St Mary’s Campus, HIV Clinical Trials Unit, Winston Churchill Wing, London W2 1NY, UK

7 Institute for Global Health and Department of Pediatrics, Vanderbilt University, Institute for Global Health, 2525 West End Avenue, Suite 750, Nashville, TN 32703, USA

8 Department of Infectious Disease Epidemiology, Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG, UK

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Trials 2014, 15:57  doi:10.1186/1745-6215-15-57

Published: 13 February 2014

Abstract

Background

Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis.

Methods/Design

A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.

In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes.

Discussion

Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT.

Trial registration

ClinicalTrials.gov NCT01900977.