Comparing clinical outcomes of antibiotics for treating Mycobacterium avium complex infection in adults with HIV: a systematic review and network meta-analysis

BACKGROUND: This study aims to identify the comparative effects of different drug regimens in treating Mycobacterium avium complex (MAC). METHODS: PubMed, EMBASE, CENTRAL, and EBSCO Open Dissertations were searched in September 2023. We included randomized controlled trials in people with HIV and MAC infection that compared any regimens and reported culture- conversion results. Antibiotic regimens were classified as azithromycin plus ethambutol (AZI+E); clarithromycin plus clofazimine (CLA+CLO); clarithromycin plus ethambutol (CLA+E); clarithromycin plus ethambutol and clofazimine (CLA+E+CLO); clarithromycin plus ethambutol and rifampicin/rifabutin (CLA+E+R); clarithromycin plus rifampicin/rifabutin (CLA+R); clofazimine plus ethambutol (CLO+E); and clofazimine plus ethambutol and rifampicin/rifabutin (CLO+E+R). Risk ratios with 95% confidence interval (95% CI) were estimated using a random-effects model. The effects of treatment regimens were ranked using the surface under the cumulative ranking (SUCRA). FINDINGS: Of 3611 articles identified, 12 met ( n = 2987) the eligibility criteria. The following regimens showed higher culture-conversion outcomes (risk ratio [95%CI]) compared to CLA+E: CLA+CLO (1.15 [0.73,1.81]), CLA+E+R (1.09 [0.80,1.47]), CLA+E+CLO (1.01 [0.69,1.46]), CLA+R [0.97 (0.56,1.70]), AZI+E (0.82 [0.60,1.13]), CLO+E+R (0.44 [0.25,0.77]), CLO+E (0.37 [0.19,0.72]). The SUCRA of CLA+CLO (80.9%) aligns with its highest comparative efficacy. The RR of culture conversion to negative was higher in ARV-treated patients. Adverse events were similar across regimens, except for a higher risk with CLO+E+R compared to CLA+CLO (7.21 [1.22-42.64]). INTERPRETATION: Clarithromycin-based regimens remain the treatment of choice for MAC in people with HIV. Although clarithromycin plus clofazimine appears to be the most effective regimen, other clofazimine-based regimens should not be considered as the initial treatment choice. The effective antiretroviral improving culture-conversion outcomes.