Promoting Engagement in the Drug Resistant TB-HIV Care Continuum in South Africa PRAXIS Study

Study Overview
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Brief Summary
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The goal of the proposed study is to enhance adherence and retention in care for M/XDR-TB HIV patients through enhanced standard of care, targeted transition to outpatient medication self-administration prior to hospital discharge, and use of community adherence groups, with an overarching goal of promoting patient engagement in a care continuum.

Detailed Description
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Tuberculosis (TB) remains the leading cause of morbidity and mortality worldwide among people living with HIV (1). Globally, the incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB), the most drug-resistant forms of TB, has approximately doubled over the past fifteen years (1-3). Nowhere has this increased incidence generated more concern than in South Africa where interactions between TB and generalized HIV epidemics are causing 'explosive' TB incidence (4-6) and case-fatality are threatening to undermine the progress reached with antiretroviral therapy (ART) (7, 8). Medication adherence, a key predictor of outcomes in M/XDR-TB and HIV treatment, is understudied in high burden TB-HIV settings (9-11). Patient losses during transitions in the care continuum are frequent (12), increase mortality and limit control of the linked epidemics. Demands of M/XDR-TB HIV treatment are severe including extraordinary pill burden, severe adverse effects, lengthy treatment, isolation and stigma with few parallels in modern medicine (13-15).

Official Title
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Promoting Engagement in the Drug Resistant TB-HIV Care Continuum in South Africa PRAXIS Study (PRospective Study of Adherence in M/XDR-TB Implementation Science) Aim 2

Conditions
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Adherence, Patient

Intervention / Treatment
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* Device: Wisepill device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years MTB culture positive with at least isoniazid and rifampicin resistance OR Molecular drug susceptibility test confirming resistance to at least isoniazid and rifampicin OR Polymerase chain reaction test (Xpert MTB/RIF) result showing MTB positive and RIF resistance. OR MTB positive with Rifampicin monoresistance Initiating treatment for M/XDR-TB which includes Bedaquiline (BDQ) or Moxifloxacin/Levaquin Have capacity for informed consent HIV Positive Patients: on ART or initiating ART within the following 4 weeks as per clinician recommendation Exclusion Criteria: Pregnancy Prisoners Discretion of IOR or clinician

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Participants assigned to the control arm will undergo treatment and care for MDR/XDR-TB as per the South African Department of Health guidelines. | |
| Experimental: Intervention<br>Participants assigned to the intervention arm will undergo extensive counselling, participants will be provided with an electronic pillbox that monitors their adherence to one of their TB and one of their ART medication. Based on the recordings provided by the wisepill device we will determine if a participant is adherent to their medication and intervene with counselling, phone calls, home visits and relevant referrals. | Device: Wisepill device<br>* Participants will receive a Wisepill device for TB and ART medications. Participants will receive an exit counselling session prior to being discharged. Participants will select the content of a text message to be sent when missing a dose as measured by Wisepill non-opening during medication dose-window. Participants will receive a post-discharge phone call by study staff for the purpose of identifying any early challenges or obstacles. All participants may receive a titrated Wisepill intervention (TWI) consisting of a text message, phone call, and/or study home visit triggered by medication non-adherence as detected by Wisepill non-opening. All participants will receive a monthly counselling intervention (MCI). Adherence support groups (ASG) will be conducted on a monthly basis.<br>* Other names: Post Discharge Phone Calls;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence in M/XDR-TB HIV outcomes | The number of participants that are adherent to their TB and ARV medication as assessed by: the use of wisepill device (electronic pill box). 2 wisepill devices are provided to participants in the intervention arm, one for their ART medication and one for their TB medication (namely Bedaquiline). By self reporting via 7-day recall and 30-day recall By self reporting via Visual analogue scale | 9-24 months | 
| Retention in care | Retention in care will be assessed by loss to follow-up. | 9-24 months | 
| TB treatment outcomes | The number of participants with TB treatment outcomes as assessed by death or culture conversion. | 9-24 months |