The impact of bedaquiline and delamanid containing regimens on liver function in patients multi-infected with pulmonary DR-TB, HIV and viral hepatitis

Background: Management of drug-resistant tuberculosis (DR-TB) patients (pts) co-infected with HIV and viral hepatitis is often complicated by hepatotoxicity. Aim: To assess the effect of regimens containing bedaquiline (Bdq) and delamanid (Dlm) on liver function in a high-risk group of pts. Methods: An observational cohort study was conducted in Georgia among DR-TB pts co-infected with HIV and viral hepatitis and treated with Bdq and Dlm containing regimens. Adaptation of antiretroviral therapy (ART) and active drug safety monitoring was provided in accordance with WHO recommendations. Results: Of 586 DR-TB pts enrolled in Bdq and Dlm containing regimens in the period of July 2014 to October 2018, 21 male pts with a mean age of 42 years and mean BMI-21kg/m2, were co-infected with HIV (mean CD4 count - 227 cells/mm3( SD-154)) and HCV. Two more pts were also co-infected with HBV. All pts were on ART, 8 pts started Tx with Bdq containing scheme and 12 - with Dlm, 1 relapsed pt received a combination of Bdq and Dlm. Overall, 5 (23.8%) patients with Bdq in the Tx scheme and nevirapine-based ART developed clinically significant hepatotoxicity: 3 pts - grade III, and 2 pts - grade IV (WHO Toxicity Grades). The latter 2 already culture converted pts were switched to hepatitis “C” elimination program. None of the pts with Dlm experienced clinically significant hepatotoxicity. Culture conversion was achieved in 16 (76%) cases with a mean time of 2.3 (SD-1.6) months. Conclusion: In a high-risk group of pts for liver injury, Bdq and Dlm containing regimens showed a good efficacy and safety profile. Schemes with Dlm were the least hepatotoxic.