Background and setting: A reliable and timely clinical, radiological, and bacteriological diagnosis, and an optimal treatment of non-tubercular mycobacteriosis (including Mycobacterium xenopi disease), remain an unanswered challenge for clinicians facing immunocompromised patients, including those with HIV infection.

Objective: The aim of our survey is to report the frequency, and the epidemiological, immunological, microbiological, clinical, and therapeutic features of all confirmed HIV-associated M. xenopi disease observed from 1993–2002, with special attention paid to eventual differences that emerged after the introduction of potent antiretroviral therapy (highly active antiretroviral therapy, HAART), on the basis of an international literature update.

Design and results: Our series of 17 consecutive confirmed M. xenopi infections retrieved in 14 out of 3000 patients followed for HIV disease complications raises a broad series of clinical, diagnostic, therapeutic, and prophylactic concerns. The great majority of M. xenopi disease involved the lower respiratory tract, but atypical features including cavitation and prominent exudative features became apparent in patients successfully treated with HAART, pointing out the possible role of the so-called immune reconstitution syndrome in these episodes.

Conclusions: Diagnostic problems represented by late or missed identification due to slow culture and frequently concomitant opportunistic disorders, join therapeutic difficulties due to the unpredictable in vitro antimicrobial susceptibility profile of these organisms, selection of treatment and chemoprophylaxis according with clinical-radiological and microbiological suspicion, and concomitantly administered medications.