title: The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial.
abstract: BACKGROUND
  Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap.
  
  
  OBJECTIVE
  The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho.
  
  
  METHODS
  Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6-9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete.
  
  
  CONCLUSIONS
  The START Study evaluates a CIP targeting barriers to early ART implementation among TB/HIV patients. If the CIP is found effective and acceptable, this study has the potential to inform care for TB/HIV patients in high-burden, resource-limited countries in sub-Saharan Africa.
authors.affiliation: ICAP, Columbia University, New York, NY, USA.|Department of Epidemiology, Columbia University, New York, NY, USA; aah2138@columbia.edu.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Howard
authors.affiliation: ICAP, Columbia University, New York, NY, USA.|Department of Epidemiology, Columbia University, New York, NY, USA.
authors.forename: Yael
authors.initials: Y
authors.lastname: Hirsch-Moverman
authors.affiliation: ICAP, Columbia University, New York, NY, USA.
authors.forename: Koen
authors.initials: K
authors.lastname: Frederix
authors.affiliation: ICAP, Columbia University, New York, NY, USA.|CAPRISA, Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.|Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: Amrita
authors.initials: A
authors.lastname: Daftary
authors.affiliation: ICAP, Columbia University, New York, NY, USA.|Department of Epidemiology, Columbia University, New York, NY, USA.
authors.forename: Suzue
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Health Policy and Management, Columbia University, New York, NY, USA.
authors.forename: Tal
authors.initials: T
authors.lastname: Gross
authors.affiliation: ICAP, Columbia University, New York, NY, USA.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Lesotho Ministry of Health National Tuberculosis Program, Maseru, Lesotho.
authors.forename: Llang Bridget
authors.initials: LB
authors.lastname: Maama
keywords: TB treatment success; TB/HIV integration; acceptability; cost-effectiveness; implementation science