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 (ADAP-TIV): Study protocol for an adaptive randomized controlled trial.

Background: Highly effective, short course, bedaquiline-containing treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and integrase strand transfer inhibitor (INSTI)-containing fixed dose combination antiretroviral therapy (ART) have radically transformed treatment for MDR-TB and HIV. However, without advances in adherence support, we may not realize the full potential of these therapeutics. The primary objective of this study is to compare the effect of adherence support interventions on clinical and biological endpoints using an adaptive randomized platform. Methods: This is a prospective, adaptive, randomized controlled trial comparing the effectiveness of four adherence support strategies on a composite clinical outcome in adults with MDR-TB and HIV initiating bedaquiline-containing MDR-TB treatment regimens and receiving ART in KwaZulu-Natal, South Africa. Trial arms include 1) enhanced standard of care; 2) psychosocial support; 3) mHealth using cellular- enabled electronic dose monitoring; 4) combined mHealth and psychosocial support. The level of support will be titrated using a differentiated service delivery (DSD)-informed assessment of treatment support needs. The composite primary outcome will be include survival, negative TB culture, retention in care and undetectable HIV viral load at month 12. Secondary outcomes will include individual components of the primary outcome and quantitative evaluation of adherence on TB and HIV treatment outcomes. Discussion: This trial will evaluate the contribution of different modes of adherence support on MDR-TB and HIV outcomes with WHO recommended all-oral MDR-TB regimens and ART in a high-burden operational setting. We will also assess the utility of a DSD framework to pragmatically adjust levels of MDR-TB and HIV treatment support.

The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study.

Studies suggest that adjuvant chemotherapy for early stage breast cancer (BC) is associated with cognitive impairment related to attention, memory, and visuospatial functioning. However, other studies have failed to confirm that relationship. We report one of the first longitudinal, controlled studies of cognitive effects of chemotherapy in older post-menopausal women. Sixty-one post-menopausal women with non-metastatic BC were administered neuropsychological tests before adjuvant therapy (Time1), six months after treatment (Time2), and at a final 6-month follow-up (Time3). Thirty women were treated with chemotherapy; thirty-one women who received no chemotherapy were controls. Cognitive domains measured included motor, language, attention/concentration/working memory, visuospatial, and memory (verbal and visual). Time-by-treatment interaction was significant in the motor domain (P = 0.007) with poorer performance in women treated with chemotherapy. For the other domains, scores did not significantly vary over time by group. In post-menopausal women, chemotherapy was not associated with changes in cognitive function in areas reported by BC survivors: attention, memory, and information processing. Motor slowing in women treated with chemotherapy could be secondary to peripheral neuropathy rather than an indication of more general declines in cognitive processing. Future studies should control for the independent effects of slowed motor functioning when looking to study possible chemotherapy related cognitive processing deficits.