Clinical trial NCT03162107: Promoting Engagement in the Drug Resistant TB/HIV Care Continuum in South Africa
Official title: 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)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Patient Non-compliance
Keywords: adherence
HIV
MDR/XDR TB
Health Care Worker
Lead sponsor: Centre for the AIDS Programme of Research in South Africa
Sponsor class: NETWORK
Collaborators: name: Columbia University
First posted: 2017-05-22
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Medication adherence based on electronic monitoring
timeFrame: 6 months
Secondary outcomes:
measure: Medication adherence based on self-report
timeFrame: 6 months
measure: Sociomedical risk factors associated with six-month adherence to ART or TB medications
timeFrame: 6 months
Other outcomes:
Locations:
city: Durban
country: South Africa
facility: King Dinuzulu Hospital
state: Kwa-Zulu Natal
Study officials:
affiliation: Centre for the AIDS Programme of Research in South Africa
name: Nesri Padayatchi, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.