Promoting Engagement in the Drug Resistant TB/HIV Care Continuum in South Africa (PRAXIS)

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)

The goals of this research are to understand adherence and retention in care for multi-and extensively drug-resistant tuberculosis (M/XDR-TB) patients using a mixed methods approach.

Study Overview

• Status: Completed
• Conditions: Patient Non-compliance

Detailed Description

Tuberculosis (TB) remains the leading cause of morbidity and mortality worldwide among people living with HIV. Globally, 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. 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 and case-fatality threatening to undermine the progress reached with antiretroviral therapy (ART).

Medication adherence, a key predictor of outcomes in multi-and extensively drug-resistant tuberculosis (M/XDR-TB) and HIV treatment, is understudied in high burden TB/HIV settings. Patient losses during transitions in the care continuum are frequent, 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.

This is a prospective observational cohort study for patients newly diagnosed with M/XDR-TB initiating treatment. A mixed method approach will be employed to address the complex research questions of distilling determinants of barriers and facilitators to both TB medications and ART; this study will employ complementary qualitative and quantitative methodologies for assessing differential adherence to TB medications and ART.

A sub-set of patients and health care workers will be approached for participation in focus group discussions.

• Study Type: Observational
• Enrollment (Actual): 199

Contacts and Locations

Study Locations

• South Africa
  • Kwa-Zulu Natal
    • Durban, Kwa-Zulu Natal, South Africa
      • King Dinuzulu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with newly diagnosed active pulmonary multi- and extremely-drug resistance tuberculosis (M/XDR-TB) (≥ 18 years old), admitted for routine care at King DinuZulu Hospital in Durban, South Africa will be approached for enrollment. Only patients with capacity for consent will be included in the study. Healthcare workers will be approached for participation in focus group discussions.

Description

Inclusion Criteria:

1. Age ≥ 18 years

2. Mycobacterium Tuberculosis (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 (GeneXpert MTB/RIF) result showing MTB positive and RIF resistance. Patients enrolled with only a GeneXpert MTB/RIF result will be withdrawn if their subsequent susceptibility test or molecular drug susceptibility test reveals rifampicin monoresistance.

3. Initiating treatment for M/XDR-TB which includes at least 2 new medications
4. Have capacity for informed consent
5. HIV Positive Patients: on antiretroviral therapy (ART) or initiating ART within the following 4 weeks as per clinician recommendation

Exclusion Criteria:

1. Pregnancy
2. Prisoners
3. Discretion of the Investigator of Record or clinician

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication adherence based on electronic monitoring	An electronic monitoring system (e.g., Wisepill technologies) will be used to measure adherence to antiretroviral therapy and treatment of multi- and extremely-drug resistant tuberculosis.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medication adherence based on self-report	Quantitative adherence will be measured using 30 day and 7 day recall. Average adherence to both antiretroviral therapy and tuberculosis treatment will be calculated for each patient	6 months
Sociomedical risk factors associated with six-month adherence to ART or TB medications	Barriers and facilitators to medication adherence and retention in care for M/XDR-TB HIV patients will be identified through in-depth interviews and focus group discussions with patients and health care workers. To identify sociomedical risk factors associated with six-month adherence to ART or TB medications we will first identified risk factors associated with adherence in bivariate analysis and then multiple logistic regression models will be constructed including variables which are statistically significant and/or associated with >10% change in effect measure.	6 months

Collaborators and Investigators

• Sponsor: Centre for the AIDS Programme of Research in South Africa
• Collaborators: Columbia University
• Investigators: Principal Investigator: Nesri Padayatchi, MBChB, Centre for the AIDS Programme of Research in South Africa

Publications and helpful links

General Publications

• Bateman M, Wolf A, Chimukangara B, Brust JCM, Lessells R, Amico R, Boodhram R, Singh N, Orrell C, Friedland G, Naidoo K, Padayatchi N, O'Donnell MR. Adherence Measured Using Electronic Dose Monitoring is Associated with Emergent Antiretroviral Resistance and Poor Outcomes in People with Human Immunodeficiency Virus/AIDS and Multidrug-Resistant Tuberculosis. Clin Infect Dis. 2022 Oct 29;75(9):1489-1496. doi: 10.1093/cid/ciac232.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): January 10, 2020
• Study Completion (Actual): August 16, 2021

Study Registration Dates

• First Submitted: March 24, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: HIV; adherence; Health Care Worker; MDR/XDR TB
• Other Study ID Numbers: CAP 086

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No