Start TB Patients on ART and Retain on Treatment (START Study)

Study Overview
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Brief Summary
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The purpose of the START Study is to identify an effective, cost-effective, acceptable intervention that addresses programmatic, structural and psychosocial barriers to ART initiation and retention during TB treatment, with the ultimate goal of improving health outcomes among HIV-infected TB patients in Lesotho. The study is a two-arm cluster randomized trial, randomized at the TB/HIV clinic level, which includes twelve TB/HIV clinics in Berea district. Clinics are randomized to deliver the combination intervention package (CIP) or standard of care (SOC), with stratification by facility type. The experimental intervention will be delivered to all HIV-infected TB patients in TB/HIV clinics randomly assigned to CIP. In TB/HIV clinics assigned to SOC, usual care procedures for ART initiation and retention will be delivered. Study hypotheses focus on the effectiveness of the CIP on HIV- and TB-related outcomes. Compared to HIV-infected TB patients attending SOC clinics, HIV-infected TB patients at CIP clinics will have superior HIV- and TB-related outcomes, including: Greater ART initiation during TB treatment Shorter time to ART initiation Greater retention in ART care Higher adherence to ART Greater change in CD4+ count Greater TB treatment success (completion and cure) Greater sputum smear conversion Higher adherence to TB treatment Additionally, CIP delivery will have an incremental cost-effectiveness ratio more favorable than alternative resource uses.

Detailed Description
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Among people living with HIV (PLWH), tuberculosis (TB) is the most common opportunistic illness and a leading cause of death, accounting for nearly a quarter of HIV-related deaths worldwide. Initiating antiretroviral therapy (ART) early during TB treatment significantly increases survival, and World Health Organization (WHO) guidelines recommend ART initiation for all PLWH as soon as possible after TB treatment initiation, regardless of CD4+ count. Yet in the African Region, only 42% of TB patients known to be living with HIV were on ART in 2010, and retention in ART programs has been limited. In Lesotho, only 27% of HIVinfected TB patients received ART in 2010. There is an urgent need to identify programmatic interventions that increase the proportion of HIV-infected TB patients on ART, shorten the duration between TB diagnosis and ART initiation, and improve adherence to medications and retention in care amongst HIV-infected TB patients in Lesotho. Lesotho, a small, landlocked country completely surrounded by South Africa, is among the world's poorest nations with one of the world's most severe epidemics of HIV and tuberculosis (TB). There is strong evidence that TB patients who are also infected with HIV have better survival rates if they begin antiretroviral therapy (ART) soon after starting TB treatment; however, there are many patients who do not initiate ART within the recommended timeframe, and who do not remain in care.

Official Title
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Start TB Patients on ART and Retain on Treatment: Combination Intervention Package to Enhance Antiretroviral Therapy Uptake and Retention During TB Treatment in Lesotho

Conditions
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Tuberculosis, HIV

Intervention / Treatment
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* Other: Combination Intervention Package
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Measurement Cohort Participant Inclusion Criteria: HIV-infected On TB treatment Initiating ART within 2 months of TB treatment initiation Aged 18 or older English- or Sesotho-speaking Capable of informed consent Measurement Cohort Participant Exclusion Criteria: Children under age of 18 Patients diagnosed with Multi Drug Resistant-TB (MDR-TB) Key Informats: Three groups of key informats (KI) will be recruited. Key Informants ART Early-Initiators Inclusion Criteria: A measurement cohort participant Initiaing ART within the first 8 weeks of TB treatment Key Informants ART Non/Late-Initiators Inclusion Criteria: A measurement cohort participant did not initiate ART during TB treatment or initiating ART >= 2 months after TB treatment initiation Key Informants Healthcare Workers Inclusion Criteria: Nurse or VHW working in a CIP clinic or VHW working in the community and affiliated with CIP clinic Aged 18 or older English- or Sesotho-speaking Capable informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CIP Participants<br>Participants will receive the usual procedures (standard of care) for management of HIV-infected TB patients, and in addition the Combination Intervention Package (CIP) with the programmatic, structural, and psychosocial components. | Other: Combination Intervention Package<br>* CIP will contain programmatic, structural and psychosocial components including: 1) nurse training and mentorship in TB/HIV cotreatment using a clinical algorithm; 2) reimbursement of transportation costs to monthly clinic visits for patients and treatment supporters; 3) health education using a TB and HIV treatment literacy curriculum for patients and treatment supporters; and 4) real-time adherence support using short message service (SMS) text messaging and trained village health workers (VHW). These components were selected for their promise, practicality, and feasibility of implementation and scale-up in HIV programs in diverse settings - in addition to SOC.<br>* Other names: CIP;|
| Other: SOC Participants<br>Participants will receive the usual procedures (standard of care) for management of HIV-infected TB patients. TB and HIV services are fully integrated in a one-stop model, while at hospitals, ART is provided in the TB clinic for TB/HIV coinfected patients. | Other: Standard of Care<br>* Usual procedures for management of HIV-infected TB patients will be followed: Three I's training, ART provision to TB patients in integrated clinics, and treatment supporter for TB treatment.<br>* Other names: SOC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of TB/HIV patients newly registered during period of observation who initiate ART during TB treatment | To examine ART initiation based on review of clinic registers. | Up to 9 months | 
| Percentage of participants who attended 6 month clinic visit (within 1 month window) and reported ART use | To examine ART retention. Deaths and transfers will be considered not retained. | Up to 6 months after TB treatment initiation | 
| Participants with cure + treatment completion at end of TB treatment | To examine TB treatment success as defined by WHO, based on review of TB register and treatment cards. | Up to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days from TB treatment initiation to date of ART initiation | To examine Time to ART initiation | Up to 9 months | 
| Percentage of total prescribed doses ingested for ART | To examine ART adherence, averaged across medicines for each month of treatment, from the unannounced pill counts. | Up to 9 months | 
| Change in CD4+ count | To examine change in CD4 count over 6 months (from initiation of TB treatment to 6 months later). Routine clinical CD4 test results will be used by study staff and no additional blood draw will be required. | Up to 6 months after initial CD4 count | 
| Percentage of smear positive pulmonary TB cases that converted to smear negative after eight weeks of treatment | To examine sputum smear conversion | Up to 8 weeks from initiation of TB treatment | 
| Percentage of total prescribed doses ingested for TB treatment | To examine TB treatment adherence, from unannounced pill counts. | Up to 9 months | 
| Ratio of the incremental costs of the CIP to incremental effectiveness | To examine incremental cost-effectiveness of CIP (per ART initiation, retention, and TB treatment completion) | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lesotho, TB, tuberculosis, HIV, antiretroviral therapy, ART, adherence, combination intervention package, retention