Safety of bedaquiline for treatment of MDR/XDR tuberculosis in HIV co-infected patients

<b>Background:</b> The use of Bedaquiline-containing regimens improves outcomes of treatment, but the safety of bedaquiline (Bdq) in HIV patients is not enough studied. The aim was to analyze the frequency and severity of adverse drug reactions (ADRs) during bedaquiline-containing anti-tuberculosis therapy (ATT) in HIV/TB co-infected patients. <b>Methods:</b> 57 HIV co-infected patients with drug-resistant pulmonary TB (71.9% male, med 36 y.o., MDR in 21, XDR in 34) were monitored for ADRs during the first 6 month of ATT including Bdq (regimens were formed according to WHO recommendations). 56 were culture-positive; 13 had extrapulmonary TB; 56 (98.2%) – HIV infection of grade 4, with baseline СD4+ level of 11-1745 (med 171); all received antiretroviral therapy (either first- or second-line regimens without considering Bdq use). ADRs having DMID Grade 3-4 were recorded as serious. <b>Results:</b> only 8 patients (14.0%, 95%CI 7.0-25.6%) experienced at least one ADR, to a total of 10 events: 5 – gastrointestinal disorders, 1 – clinically significant sinus bradycardia (45-50 heart beats/min), 1 – QTcF prolongation (512 ms) with episodes of non-sustained “torsades de pointes” (the patient received Bdq, moxifloxacin and azithromycin simultaneously), 1 – deafness, 1 – hepatitis and 1 – tendinopathy. SADR were registered in 3 pts (5.3%, 95%CI 1.2-14.9%). Bdq was discontinued due to ADR in 4 pts (7.0%), 2 with QTcF prolongation/bradycardia and 2 with gastrointestinal disorders. <b>Conclusion:</b> bedaquiline-containing regimens appear to show reassuring safety profile with low frequency of serious adverse reactions.