Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa

Project Summary/Abstract Tuberculosis (TB) is the leading cause of mortality among people living with HIV, causing one in three deaths world-wide. In southern Africa, interaction between TB and HIV epidemics has led to increased transmission of drug-resistant TB (DR-TB), critically undermining both TB and HIV- related treatment targets. Bedaquiline (BDQ) is the first new TB drug in over 40 years, and the World Health Organization recommends the inclusion of BDQ in DR-TB treatment allowing for more effective, entirely oral DR-TB treatment. Despite challenges, BDQ rollout in South Africa has been highly successful in reducing TB associated-mortality and improving cure rates. Dolutegravir, an integrase strand transfer inhibitor, formulated as part of a once-daily combination antiretroviral therapy (ART), is newly available in the South African public health system. Tenofovir/lamivudine/dolutegravir (TLD) is superior to older comparator regimens, protective for discontinuation due to adverse events, and has minimal interaction with BDQ. The availability of TLD and BDQ has radically transformed the treatment paradigm for DR-TB HIV but advances in dual adherence support are needed to realize the benefits of new therapeutics for patients, and to prevent emergent resistance. Patient-centered adherence support strategies using psychosocial support and mHealth (health practices supported by mobile technologies) approaches may improve DR-TB HIV outcomes. The goal of the proposed study is to evaluate an integrated intervention to enhance adherence to BDQ and TLD. Using a Bayesian, adaptive randomized trial design, this project will efficiently evaluate the relative contribution of psychosocial support and cellular-supported mHealth adherence support, in combination and separately, to improve clinical and biological outcomes for HIV and TB. BDQ adherence measured using cellular-enabled electronic pill boxes, will allow us to determine optimal adherence thresholds associated with TB culture conversion. We will use a model-based approach to characterize socio-behavioral mechanisms of action for the different intervention arms (including potential non-response), and modifiable factors that present barriers and facilitators to adherence. We will also evaluate the effect of DR-TB HIV intersectional stigma on adherence. Qualitative methods will allow for longitudinal description of patient- centered treatment pathways. Once completed, this study will meet the expressed need of the South African health system for evidence-based DR-TB HIV adherence interventions and contribute generalizable knowledge about the relative contributions of adherence support modalities in medically complex patients.