Review
Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy

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Summary

Disseminated Mycobacterium avium complex (MAC) infection is a common complication of late-stage HIV-1 infection. Since the advent of highly active antiretroviral therapy (HAART), the rate of MAC infection has declined substantially, but patients with low CD4 cell counts remain at risk. Among patients in the Johns Hopkins cohort with advanced HIV disease, the proportion developing MAC has fallen from 16% before 1996 to 4% after 1996, with a current rate of less than 1% per year. Factors associated with developing MAC include younger age, no use of HAART, and enrolment before 1996. Prophylaxis with azithromycin or clarithromycin is recommended for all patients with CD4 counts less than 50 cells/mL. Optimum treatment for disseminated MAC includes clarithromycin and ethambutol, and another investigation suggests that the addition of rifabutin might reduce mortality. Both prophylaxis and treatment of disseminated MAC can be discontinued in patients who have responded to HAART, and specific guidelines for withdrawing treatment have been published. Although HAART has altered the frequency and outcome of MAC infection, it remains an important complication of AIDS.

Section snippets

Clinical features and the effect of HAART

Soon after inhalation or ingestion of MAC organisms from the environment, the infection spreads via local lymphatics, eventually disseminating haematogenously.8 The bacteria are taken up by mononuclear phagocytic cells throughout the body, and reticuloendothelial organs such as the liver, spleen, and bone marrow are the most frequently affected sites.8 Consequently, the clinical presentation of disseminated MAC commonly includes fever, weight loss, night sweats, fatigue, diarrhoea,

Prophylaxis Criteria for initiating primary prophylaxis

Before the development of effective chemoprophylaxis, up to 40% of HIV-infected patients developed disseminated MAC within 2 years of the diagnosis of AIDS.1, 2 HIV-infected adults who have a CD4 cell count of less than 50 cells/mL are at heightened risk for MAC infection and should receive chemoprophylaxis (table 2).18 Although official guidelines do not include criteria for prophylaxis on the basis of HIV plasma RNA (viral load) measurements, it seems that patients with high viral loads are

Regimens

Rifabutin, a semi-synthetic rifamycin with substantial activity against MAC in vitro and in animal models,21, 22 was the first drug found to have some benefit in preventing MAC infection in patients with AIDS.23 Two multicentre, randomised, double-blind, placebo-controlled trials showed that rifabutin (300 mg daily) prophylaxis significantly reduced the rate of MAC bacteraemia from 17–18% to 8–9% in patients with AIDS.23 Additionally, rifabutin prophylaxis was associated with a significant

Discontinuation of primary prophylaxis

Because of concerns about potential incomplete restoration of immunological function in patients whose CD4 cell count rose significantly in response to antiretroviral therapy,36 earlier guidelines recommended indefinite continuation of primary prophylaxis for MAC infection.37 Subsequent studies have investigated the safety of discontinuing primary chemoprophylaxis against MAC in patients whose CD4 cell counts, in response to HAART, have risen above threshold values for the initiation of

Treatment

A major advance in the treatment for disseminated MAC was the recognition of the in-vivo efficacy of clarithromycin, which is now regarded as the cornerstone of any potent regimen.40, 41 ACTG 157 was a randomised, double-blind, dose-ranging study in HIV-infected patients with MAC bacteraemia who were assigned to three different dosage regimens of clarithromycin (500, 1000, and 2000 mg twice daily) for 12 weeks.40 Time to clearance of bacteraemia was faster at higher doses but was equivalent in

Future directions

Significant progress has been made in the last decade in the treatment of HIV and in the prevention and treatment of various opportunistic infections, including MAC. These advances have resulted in a diminished rate of MAC infection in developed countries. However, MAC continues to occur frequently in areas of the world where HAART is unavailable, or in patients who do not have access to or who cannot tolerate HAART, or who have developed drugresistant HIV infection. For these patients, MAC

Search strategy and selection criteria

Data for this review were identified by searches of Medline and references from relevant articles; numerous articles were identified through searches of the authors'extensive files. Search terms were “Mycobacterium avium complex”, “Thrapy”, “prophylaxis”, “clinical trials”, “guidelines”, “human immunodeficiency virus”, “acquired immunodeficiency syndrome”, “highly active antiretroviral-drug therapy”, “macrolides”, “clarithromycin”, “azithromycin”, “rifabutin”, “fluoroquinolones”, and

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      Night sweats, diarrhoea, nausea and vomiting, and abdominal pain have also been reported [1,4]. Laboratory tests may show anaemia and elevated levels of alkaline phosphatase and lactate dehydrogenase [1,5]. A rise in SGOT, SGPT was reported in this case, which could be part of granulomatous hepatitis due to disseminated MAC infection.

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