Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis.

Rationale: Current recommendations for the treatment of rifampicin- and multidrug-resistant tuberculosis include bedaquiline (BDQ) used for 6 months or longer. Evidence is needed to inform the optimal duration of BDQ. Objectives: We emulated a target trial to estimate the effect of three BDQ duration treatment strategies (6, 7-11, and ⩾12 mo) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis. Methods: To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse probability weighting. Measurements and Main Results: The 1,468 eligible individuals received a median of 4 (interquartile range, 4-5) likely effective drugs. In 87.1% and 77.7% of participants, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment was 0.85 (95% confidence interval [CI], 0.81-0.88) for 6 months of BDQ, 0.77 (95% CI, 0.73-0.81) for 7-11 months, and 0.86 (95% CI, 0.83-0.88) for ⩾12 months. Compared with 6 months of BDQ, the ratio of treatment success was 0.91 (95% CI, 0.85-0.96) for 7-11 months and 1.01 (95% CI, 0.96-1.06) for ⩾12 months. Naive analyses that did not account for bias revealed a higher probability of successful treatment with ⩾12 months (ratio, 1.09 [95% CI, 1.05-1.14]). Conclusions: BDQ use beyond 6 months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person-time bias can influence estimates of the effects of treatment duration. Future analyses should explore the effect of treatment duration of BDQ and other drugs in subgroups with advanced disease and/or receiving less potent regimens.

Improving access to health services through health reform in Lesotho: Progress made towards achieving Universal Health Coverage.

In 2014 the Kingdom of Lesotho, in conjunction with Partners In Health, launched a National Health Reform with three components: 1) improved supply-side inputs based on disease burden in the catchment area of each of 70 public primary care clinics, 2) decentralization of health managerial capacity to the district level, and 3) demand-side interventions including paid village health workers. We assessed changes in the quarterly average of quality metrics from pre-National Health Reform in 2013 to 2017, which included number of women attending their first antenatal care visit, number of post-natal care visits attended, number of children fully immunized at one year of age, number of HIV tests performed, number of HIV infection cases diagnosed, and the availability of essential health commodities. The number of health centers adequately equipped to provide a facility-based delivery increased from 3% to 95% with an associated increase in facility-based deliveries from 2% to 33%. The number of women attending their first antenatal and postnatal care visits rose from 1,877 to 2,729, and 1,908 to 2,241, respectively. The number of children fully immunized at one year of life increased from 191 to 294. The number of HIV tests performed increased from 5,163 to 12,210, with the proportion of patients living with HIV lost to follow-up falling from 27% to 22%. By the end of the observation period, the availability of essential health commodities increased to 90% or above. Four years after implementation of the National Health Reform, we observed increases in antenatal and post-natal care, and facility-based deliveries, as well as child immunization, and HIV testing and retention in care. Improved access to and utilization of primary care services are important steps toward improving health outcomes, but additional longitudinal follow-up of the reform districts will be needed.