Prevalence, treatment, and outcomes of hepatitis C in an MDR/RR-TB trial cohort.

Tuberculosis (TB) and chronic hepatitis C virus infection (HCV) remain significant global health challenges, especially in low- and middle-income countries. In Eastern Europe, a considerable percentage of multi-drug resistant (MDR) and rifampicin resistant (RR) TB populations show high HCV prevalence. Current WHO guidelines do not routinely advise HCV testing during MDR-TB treatment, despite HCV being a risk factor for drug-induced liver complications in TB patients. This study investigates the co-treatment of MDR/RR-TB and HCV, using data from the TB-PRACTECAL trial. Data were collected as part of the TB-PRACTECAL clinical trial. All participants were screened for HCV at baseline. Participants who were HCV antibody positive and those who were treated for hepatitis C with Direct Acting Antivirals (DAAs) were extracted and compared to overall cohort characteristics. The characteristics of participants concomitantly treated with direct-acting antivirals are described including hepatitis treatment outcomes and adverse events. Among 552 participants from Belarus, Uzbekistan, and South Africa, 24 (4.3%) were HCV antibody positive. Unfavourable TB treatment outcomes were noted in 106/523 (22%) of the HCV-negative, 8/18 (44%) of the HCV-seropositive, and 2/7 (29%) of HCV-confirmed participants treated with DAAs. Of the six participants who received concurrent HCV and MDR/RR TB treatment, three were cured of HCV and three had no post-treatment HCV RNA test, five completed TB treatment and one discontinued treatment due to a severe adverse reaction. Concurrent treatment of MDR-TB and HCV, including in HIV patients, showed promising outcomes with no significant adverse events. The findings support the potential benefits of integrating HCV care into MDR-TB management.

How much should we still worry about QTc prolongation in rifampicin-resistant tuberculosis? ECG findings from TB-PRACTECAL clinical trial.

Regimens for the treatment of rifampicin-resistant tuberculosis currently rely on the use of QT-prolonging agents. Using data from the randomized controlled trial, TB-PRACTECAL, we investigated differences in QTcF among participants in the three interventional arms: BPaL (bedaquiline, pretomanid, and linezolid), BPaLC (BPaL with clofazimine), and BPaLM (BPaL with moxifloxacin). Additionally, we assessed whether age, body mass index, and country were causally associated with QTcF prolongation. The trial included participants from South Africa, Uzbekistan, and Belarus. A post hoc analysis of electrocardiogram data was undertaken. Random effects regression was used to model QTcF longitudinally over 24 weeks and causal frameworks guided the analysis of non-randomized independent variables. 328 participants were included in BPaL-based arms. The longitudinal analysis of investigational arms showed an initial QTcF steep increase in the first week. QTcF trajectories between weeks 2 and 24 differed slightly by regimen, with highest mean peak for BPaLC (QTcF 446.5 ms). Overall, there were 397 QTcF >450 ms (of 3,744) and only one QTcF >500 ms. The odds of QTcF >450 ms among participants in any investigational arm, was 8.33 times higher in Uzbekistan compared to Belarus (95% confidence interval: 3.25-21.33). No effect on QTcF prolongation was found for baseline age or body mass index (BMI). Clinically significant QTc prolongation was rare in this cohort of closely monitored participants. Across BPaL-based regimens, BPaLC showed a slightly longer and sustained effect on QTcF prolongation, but the differences (both in magnitude of change and trajectory over time) were clinically unimportant. The disparity in the risk of QTc prolongation across countries would be an important factor to further investigate when evaluating monitoring strategies. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT02589782.

Treatment Compliance of Multidrug Resistant Tuberculosis in Uzbekistan: Does Practice Follow Policy?

Compliance with treatment guidelines is essential to achieve successful outcomes in tuberculosis patients. Thus, we assessed if multidrug-resistant tuberculosis treatment practices from 2012-2018 in Uzbekistan were compliant with national guidelines in terms of regimens prescribed, weight-based drug dosages used, and documentation of treatment changes (such as prolongation of intensive phase, change of drugs, and their reasons) in the treatment card and Consilium form. A total of 1481 patients were included. Of them, only 25% received standardized regimens as per guidelines and the remaining received individualized regimens. There was an increasing trend in using standardized regimens from 2% in 2012 to 44% in 2018. Compliance to recommended weight-based drug dosages was observed in 85% of the patients during the intensive phase and 84% in the continuation phase-ranged 71-91% over the years. Prolongation of the intensive phase was done in 42% of patients. The treatment was changed in 44% of patients during the intensive phase and 34% of patients during the continuation phase. The documentation of treatment changes was suboptimal (42-75%) during the initial years (2012-2014); however, it improved significantly during later years (86-100%). Future research should explore reasons for non-compliance so that the quality of patient care can be improved.