the start study Start TB patients on ART and Retain on Treatment

Outline 1.Background and Rationale 2.Study Aims 3.Study Design 4.Study Interventions 5.Study Sites 6.Study Participants 7.Study Measures and Outcomes 8.Collaboration 9.Capacity Building 10.Progress to date 11.Upcoming activities

Background and Rationale TB is a leading cause of death, accounts for nearly a quarter of HIV-related deaths worldwide Early initiation of ART during TB treatment significantly increases AIDS-free survival by % 1-3 In the African Region only 42% of TB patients were on ART in 2010 – In Lesotho it was as low as 27% in 2010 Need to identify programmatic interventions that can increase the number of TB/HIV patients starting ART early 1 Karim 2011; 2 Havlir 2011; 3 Blanc 2011

Study Aims Overall Aim: To identify an effective, cost-effective, acceptable intervention that addresses programmatic, structural and psychosocial barriers to ART initiation and retention during TB treatment

Study Aims (2) Specific Aim 1: To evaluate the effectiveness of integrating a combination intervention package (CIP) for ART provision during TB treatment HIV-related outcomesTB-related outcomes 1.ART initiation during TB treatment 2.Time to ART initiation 3.Retention in ART care 4.Adherence to ART 5.Change in CD4+ count 1.TB treatment success (completion & cure) 2.Sputum smear conversion 3.Adherence to TB treatment

Study Aims (3) Specific Aim 2: To assess the cost-effectiveness (incremental cost per health adjusted life-year gained) of CIP Specific Aim 3: To assess provider and patient acceptability of CIP for ART provision during TB treatment Specific Aim 4: To describe the safety and tolerability of ART during TB treatment under programmatic conditions

Study Design Two-arm cluster randomized trial, randomized at the TB/HIV clinic level Twelve TB/HIV clinics at health centers in Berea district, Lesotho Clinics randomized to deliver CIP or standard of care (SOC) – Stratification by facility type (hospital or health center)

Study Interventions: SOC vs. CIP Comparison of SOC and CIP SOCCIP Three I's training XX ART provision to TB patients in integrated clinics XX Treatment supporter for TB treatment XX TB/HIV training according to clinical algorithm X Health education for patients and treatment supporters using TB/HIV treatment literacy curriculum X Reimbursement of transportation costs X Real time adherence support with SMS messaging and VHW X

Study Sites 12 Study Sites in Berea District, Lesotho Berea Hospital Maluti Hospital Good Shepherd HC Holy Family HC Khubetsoana HC Koali HC Kolojane HC Pilot HC Sebedia HC St David HC St Magdalena HC St Theresa HC HC=health center

Study Participants All newly registered TB/HIV patients Measurement cohort of ART initiators (with 6-9 months follow up) – CIP (n=192) – SOC (n=192) Key informant interviews at CIP sites – ART non-initiators (n=30) – ART initiators (n=30) – Health care workers (n=30)

Study Outcomes All TB/HIV Patients Measurement Cohort KI ART Initiators KI ART Non- Initiators KI Healthcare Workers STUDY OUTCOMES ART initiationX Retention in ART care X Time to ART initiationX Adherence to ART X Change in CD4+ count X TB treatment successX Sputum smear conversionX Adherence to TB treatment X Side effects/adverse events X Acceptability of intervention XXX Reasons for ART non-initiation X Incremental cost per health adjusted life-year gained X

Study Measures All TB/HIV Patients Measurement Cohort KI ART Initiators KI ART Non- Initiators KI Healthcare Workers STUDY MEASURES Participants’ contact information X Baseline interview X Monthly interview X End-of-treatment interview X Unannounced pill counts X Prescription refills X Medical record abstraction X Clinic records reviewX Program characteristicsX Key Informant Interview- Patient XX Key Informant Interview-HCW X

Collaboration Ministry of Health and Social Welfare National University of Lesotho (NUL) Stakeholders Advisory Group – MOHSW, Christian Health Association of Lesotho, Lesotho Red Cross, NUL, USAID, PEPFAR, CDC, WHO, UNAIDS, Basotho community

Capacity Building Improve the research capacity of national and local institutions via training and mentorship – Situation analysis to identify gaps – Training and mentorship on: protocol development data collection data analysis, synthesis, and interpretation scientific communication – Opportunities to attend regional and international conferences – Opportunities to attend Epidemiology and Population Health Summer Institute (EPIC) at Columbia University.

Progress to date Recruitment of study staff(Research Assistants) RAs have gone through motor bike training Received approval letter from NH-IRB & NH- ERC Procurement of all study equipment is in place (Vehicle, motor bikes, computers and Printers Sensitization of DHMT and selected Selection of Lead VHWs

Upcoming activities Training of Research Assistants Training of VHWs Training of Nurses Deployment & Introduction of study team in Berea DHMT and Study facilities Launch of the study and enrolment patients

TB Register

ART Register

ICAP Officials & START team after motor bike training