Search

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.)

A 10-year review of disseminated Mycobacterium avium complex (MAC) infection and MAC-immune reconstitution inflammatory syndrome in HIV-positive patients (2004-2014) at a state-wide tertiary referral HIV service demonstrates that despite advances in antiretroviral therapy, MAC infection remains a therapeutic challenge, particularly intra-abdominal disease.

We present the case of a 55-year-old-man with AIDS who had disseminated Mycobacterium avium-intracellulare (MAI) infection who was nonadherent to antiretroviral treatment and prophylaxis for opportunistic infections. The patient acquired HIV via intravenous drug sue; he had a CD4+ cell count of 4/microL (1%) and an HIV RNA level of 114,000 copies/mL at the time of his HIV diagnosis. He presented with MAI bacteremia and had rapidly evolving and resolving cutaneous lesions caused by MAI. Concomitant nonspecific brain lesions presented a diagnostic challenge, but they improved with MAI treatment. In persons with HIV/AIDS who have cutaneous lesions, biopsy of superficial lesions has proved helpful. MAI infection should be considered in the differential diagnosis of cutaneous and brain lesions in persons with HIV/AIDS.

A rapidly progressive, fatal recrudescence of pulmonary Kaposi sarcoma developed in an HIV-infected man who was receiving corticosteroids for treatment of an immune reconstitution syndrome secondary to Mycobacterium avium complex pulmonary infection. We discuss the implications for current diagnosis and management of HIV-associated pulmonary diseases.

The role that colonization with Mycobacterium avium plays in the development of disseminated disease is unclear. In this study, we determined whether all M. avium strains isolated from the portals of M. avium infection are capable of crossing the mucosal border and causing infection. The patients in this study were enrolled in AIDS Clinical Trial Group protocol 341. The patients were divided into 3 groups; 2 groups differed in their immunological and clinical risk for M. avium disease. A third group (n=22 patients) had culture-documented disseminated M. avium complex disease at the time of entry in the study. Eight of 22 patients had M. avium isolated from both a colonized site and blood or bone marrow specimens. All 8 patients had distinct M. avium strains; 2 patients had a polyclonal infection. The virulence properties of 13 strains were determined, including invasion of gastrointestinal cells and replication in macrophages. There were significant differences in the virulence properties, and these differences may provide insight into the interplay between microbial pathogenesis and host defense.

Mycobacterium avium is a common pathogen in AIDS patients that is primarily (but not exclusively) acquired through the gastrointestinal tract, leading to the development of bacteraemia and disseminated disease. To cause infection through the gut, binding and invasion of the intestinal epithelial barrier are required. To characterize this process further, we determined the cell surface(s) (basolateral vs. apical membrane) that M. avium interacts with in intestinal mucosal cells in vitro. The level of binding and invasion of both HT-29 and Caco-2 intestinal cell monolayers by M. avium were similar when the assay was performed with control medium in the presence of Ca2+ (when only the apical surface was exposed), with Ca2+-depleted medium or with Ca2+-depleted medium + 1 mM EGTA (exposure of both apical and basolateral membranes), suggesting that the bacterium enters the apical surface of the epithelial lining. These observations were confirmed by assays in a transwell system and by using fluorescent microscopy. Real-time video microscopy showed that M. avium entry was not associated with membrane ruffling and the use of pharmacological inhibitors of the small GTPases demonstrated that M. avium invasion is dependent on the activation of the small GTPases Rho, but not on Rac or Cdc42. Passage of M. avium through HT-29 cells led to a phenotypic change (intracellular growth; IG) that was associated with a significantly greater (between five- and ninefold) ability to bind to and invade new monolayers of epithelial cells or macrophages when compared with the invasion by M. avium grown on agar (extracellular growth; EG). IG phenotype invasion of HT-29 cells also takes place only by the apical surface. M. avium enters intestinal epithelial cells by the apical surface and, once within the cells, changes phenotype, becoming more invasive towards both macrophages and other epithelial cells.

Sequence analysis of the ribosomal internal transcribed spacer of 56 Mycobacterium avium complex isolates from pediatric patients with AIDS or lymphadenitis revealed (similar to the situation in adults) that the closely related Mav-B and Mav-A sequevars caused the vast majority of disease. IS1245 restriction fragment-polymorphism analysis and pulsed-field gel electrophoresis revealed sets of isolates with closely related patterns among strains from patients in the Boston area and among isolates from Los Angeles and Miami patients. The finding of related strains that cause disease in epidemiologically unrelated patients is most consistent with one of two hypotheses: (1) a limited subset of M. avium strains is more virulent and therefore more likely to cause disease in humans, or (2) pathogenic strains are more prevalent in the environment.

One of the most important opportunistic pathogens associated with AIDS is the Mycobacterium avium complex. M. avium infections are found in up to 70% of individuals in advanced stages of AIDS. The deficiency in our knowledge of these mycobacteria presents an obstacle to the development of a rational approach for controlling these life-threatening infections in immunocompromised persons. It is apparent that M. avium can replicate in host macrophages and persist for long periods. During this time, various components, particularly lipids, accumulate in host macrophages and contribute to the ability of this organism to upset the cytokine homeostasis necessary for controlling infections of this type. M. avium lipids are immunosuppressive and can induce a variety of cytokines and eicosanoids that affect general host responses. The intention of this review is to examine the postphagocytic processing of various M. avium lipids with respect to their ability to alter host responses, particularly in immunocompromised patients such as those infected with HIV.

The incidence of identification of nontuberculous mycobacteria has increased since the advent of the acquired immunodeficiency syndrome epidemic. Although Mycobacterium avium complex appears to be responsible for most episodes of nontuberculous disease, several other previously rare species are increasingly being detected, including Mycobacterium kansasii, Mycobacterium fortuitum/chelonei complex, and Mycobacterium genavense. This review briefly summarizes the epidemiology and clinical features of these infections, as well as therapeutic and preventive strategies in immunosuppressed patients with nontuberculous mycobacterial infections. Of clinical relevance, nontuberculous mycobacterial infections are difficult to treat and do not respond to traditional antituberculous agents. The search for more effective treatment regimens is ongoing in an attempt to enhance survival and reduce morbidity among immunocompromised patients. Novel antimicrobial combinations that include clarithromycin or azithromycin have been shown to be effective in treating several nontuberculous mycobacterial infections.

Mycobacterium avium complex (MAC) strains from AIDS and non-AIDS patients and from the environment were studied for their colony morphology and virulence in beige mice. The majority of the MAC isolates from AIDS patients, in contrast to those from non-AIDS patients and the environment, showed increased virulence. Similarly, the majority of the MAC isolates from AIDS patients formed smooth transparent (ST) colonies, whereas most of the non-AIDS isolates formed smooth opaque (SO) or intermediate (IM) type of colonies. MAC isolates from the same AIDS patient obtained at different times were found to be heterogenic with respect to serotype, RFLP and glycolipid patterns, suggesting that these patients might be infected with more than one strain of MAC.