How do I manage disseminated Mycobacterium avium complex disease in people with HIV?

Background: Advanced HIV disease (AHD) is increasing, with late presentation accounting for half of newly diagnosed people with HIV (PWH) in Europe. Mortality in late-presenting PWH remains high, and Mycobacterium avium complex (MAC) disease, among other opportunistic infections, presents several diagnostic and treatment challenges that lead, ultimately, to a poor clinical outcome. Objectives: We aimed to provide guidance on the diagnosis and treatment of disseminated MAC disease (dMACd) in PWH. Sources: We performed a review of original articles, meta-analyses, and systematic reviews retrieved from PubMed. Content: We reviewed and discussed the most challenging steps in the management of PWH with AHD and dMACd: the current epidemiology in the era of effective antiretroviral treatment; clinical presentation and interpretation of symptoms in the context of other opportunistic infections and immune reconstitution; diagnosis, sampling, and timing to reach a definitive diagnosis; prophylaxis, treatment options, and indications for discontinuing MAC treatment; future perspectives; and the role of rifamycins in the treatment of dMACd. Implications: Despite the widespread availability of effective antiretroviral treatment, dMACd still represents a major cause of morbidity and mortality in PWH with AHD. Residual challenges are mainly related to the difficulties and timing required to reach a definitive diagnosis, and the discussion regarding the role of rifamycins in the treatment of dMACd is still open.