title: 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.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01900977.
authors: Richard
authors: R
authors: Hayes
authors: Helen
authors: H
authors: Ayles
authors: Nulda
authors: N
authors: Beyers
authors: Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. kalpana.sabapathy@lshtm.ac.uk.
authors: Kalpana
authors: K
authors: Sabapathy
authors: Sian
authors: S
authors: Floyd
authors: Kwame
authors: K
authors: Shanaube
authors: Peter
authors: P
authors: Bock
authors: Sam
authors: S
authors: Griffith
authors: Ayana
authors: A
authors: Moore
authors: Deborah
authors: D
authors: Watson-Jones
authors: Christophe
authors: C
authors: Fraser
authors: Sten H
authors: SH
authors: Vermund
authors: Sarah
authors: S
authors: Fidler
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000191:economics; D002944:Circumcision, Male / Q000191:economics; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000191:economics / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D017048:Health Care Costs; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening / Q000191:economics / Q000379:methods*; D011237:Predictive Value of Tests; D015995:Prevalence; D012107:Research Design; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D015024:Zambia / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents