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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., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Non-tuberculous mycobacteria (NTM) cause skin infections, respiratory diseases, and disseminated infections. Mycobacterium avium and Mycobacterium intracellulare, which are slow grown Mycobacterium, are main agents of those NTM diseases. A silkworm infection model with Mycobacterium abscessus, a rapidly growing Mycobacterium species, was established to quantitatively evaluate its virulence within a short period. However, a silkworm infection model to quantitatively evaluate the virulence of M. intracellulare has not yet been developed. In this study, we determined the virulence of M. intracellulare subspecies within 4 days using a silkworm infection model. The subspecies of M. intracellulare strains used in this study were estimated by phylogenetic tree analysis using core gene data. The median lethal dose (LD 50 ) values, which are the dose of a pathogen required to kill half of the silkworms in a group, were determined 4 days after infection. The LD 50 value of M. intracellulare subsp. chimaera DSM44623 was higher than that of M. intracellulare subsp. intracellulare ATCC13950. These results suggest that the virulence of M. intracellulare subspecies can be compared using a silkworm model within 4 days.