Mycobacterium avium complex (MAC) infections in HIV-infected patients
- Judith S Currier, MD
Judith S Currier, MD
- Professor of Medicine
- University of California, Los Angeles
Mycobacterium avium complex (MAC) refers to infections caused by one of two nontuberculous mycobacterial species, either M. avium or M. intracellulare. (See "Microbiology of nontuberculous mycobacteria".)
While infections with these organisms can occur in patients who are not HIV-infected, the frequency of infection increased and the nomenclature MAC was developed early in the HIV epidemic. Dramatic declines in the rate of new MAC cases in HIV-infected patients have accompanied the use of more effective antiretroviral therapy (ART) and the more widespread use of prophylaxis against MAC infection [1-3]. (See "Overview of prevention of opportunistic infections in HIV-infected patients" and "Epidemiology of nontuberculous mycobacterial infections".)
The epidemiology and clinical manifestations of MAC infection and current knowledge about the prevention and therapy of MAC in HIV disease will be reviewed here. MAC infections in patients without HIV are discussed separately. (See "Overview of nontuberculous mycobacterial infections in HIV-negative patients" and "Treatment of nontuberculous mycobacterial infections of the lung in HIV-negative patients".)
Transmission — Mycobacterium avium complex organisms are ubiquitous in the environment, including water and soil . The mode of infection for MAC infection is thought to be through inhalation or ingestion.
Person-to-person or common source transmission of MAC does not appear to be common; there is no need for isolation of hospitalized patients with MAC infection.
- Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338:853.
- Karakousis PC, Moore RD, Chaisson RE. Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy. Lancet Infect Dis 2004; 4:557.
- Sungkanuparph S, Vibhagool A, Mootsikapun P, et al. Opportunistic infections after the initiation of highly active antiretroviral therapy in advanced AIDS patients in an area with a high prevalence of tuberculosis. AIDS 2003; 17:2129.
- Reed C, von Reyn CF, Chamblee S, et al. Environmental risk factors for infection with Mycobacterium avium complex. Am J Epidemiol 2006; 164:32.
- Carbonne A, Lemaitre N, Bochet M, et al. Mycobacterium avium complex common-source or cross-infection in AIDS patients attending the same day-care facility. Infect Control Hosp Epidemiol 1998; 19:784.
- Swanson DS, Pan X, Kline MW, et al. Genetic diversity among Mycobacterium avium complex strains recovered from children with and without human immunodeficiency virus infection. J Infect Dis 1998; 178:776.
- Horsburgh CR Jr, Schoenfelder JR, Gordin FM, et al. Geographic and seasonal variation in Mycobacterium avium bacteremia among North American patients with AIDS. Am J Med Sci 1997; 313:341.
- Low N, Pfluger D, Egger M. Disseminated Mycobacterium avium complex disease in the Swiss HIV Cohort Study: increasing incidence, unchanged prognosis. AIDS 1997; 11:1165.
- Fordham von Reyn C, Arbeit RD, Tosteson AN, et al. The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group. AIDS 1996; 10:1025.
- Naik E, LeBlanc S, Tang J, et al. The complexity of HLA class II (DRB1, DQB1, DM) associations with disseminated Mycobacterium avium complex infection among HIV-1-seropositive whites. J Acquir Immune Defic Syndr 2003; 33:140.
- Ohkusu K, Bermudez LE, Nash KA, et al. Differential virulence of Mycobacterium avium strains isolated from HIV-infected patients with disseminated M. avium complex disease. J Infect Dis 2004; 190:1347.
- Wahl SM, Greenwell-Wild T, Peng G, et al. Mycobacterium avium complex augments macrophage HIV-1 production and increases CCR5 expression. Proc Natl Acad Sci U S A 1998; 95:12574.
- George S, Coffey M, Cinti S, et al. Neutrophils from AIDS patients treated with granulocyte colony-stimulating factor demonstrate enhanced killing of Mycobacterium avium. J Infect Dis 1998; 178:1530.
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on September 21, 2016).
- Chin DP, Hopewell PC, Yajko DM, et al. Mycobacterium avium complex in the respiratory or gastrointestinal tract and the risk of M. avium complex bacteremia in patients with human immunodeficiency virus infection. J Infect Dis 1994; 169:289.
- Grinsztejn B, Fandinho FC, Veloso VG, et al. Mycobacteremia in patients with the acquired immunodeficiency syndrome. Arch Intern Med 1997; 157:2359.
- Race EM, Adelson-Mitty J, Kriegel GR, et al. Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease. Lancet 1998; 351:252.
- Currier JS, Williams PL, Koletar SL, et al. Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count. A randomized, double-blind, placebo-controlled trial. AIDS Clinical Trials Group 362 Study Team. Ann Intern Med 2000; 133:493.
- Sepkowitz KA. Effect of HAART on natural history of AIDS-related opportunistic disorders. Lancet 1998; 351:228.
- Cunningham CO, Selwyn PA. Mastitis due to Mycobacterium avium complex in an HIV-infected woman taking highly active antiretroviral therapy. AIDS Patient Care STDS 2003; 17:547.
- Havlir DV, Haubrich R, Hwang J, et al. Human immunodeficiency virus replication in AIDS patients with Mycobacterium avium complex bacteremia: a case control study. California Collaborative Treatment Group. J Infect Dis 1998; 177:595.
- Kilby JM, Marques MB, Jaye DL, et al. The yield of bone marrow biopsy and culture compared with blood culture in the evaluation of HIV-infected patients for mycobacterial and fungal infections. Am J Med 1998; 104:123.
- Hussong J, Peterson LR, Warren JR, Peterson LC. Detecting disseminated Mycobacterium avium complex infections in HIV-positive patients. The usefulness of bone marrow trephine biopsy specimens, aspirate cultures, and blood cultures. Am J Clin Pathol 1998; 110:806.
- Pantongrag-Brown L, Krebs TL, Daly BD, et al. Frequency of abdominal CT findings in AIDS patients with M. avium complex bacteraemia. Clin Radiol 1998; 53:816.
- Pierce M, Crampton S, Henry D, et al. A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome. N Engl J Med 1996; 335:384.
- Oldfield EC 3rd, Fessel WJ, Dunne MW, et al. Once weekly azithromycin therapy for prevention of Mycobacterium avium complex infection in patients with AIDS: a randomized, double-blind, placebo-controlled multicenter trial. Clin Infect Dis 1998; 26:611.
- Ioannidis J, Wilkinson D. HIV: prevention of opportunistic infections. Clin Evid 2003; :809.
- Havlir DV, Dubé MP, Sattler FR, et al. Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. California Collaborative Treatment Group. N Engl J Med 1996; 335:392.
- Dunne MW, Bozzette S, McCutchan JA, et al. Efficacy of azithromycin in prevention of Pneumocystis carinii pneumonia: a randomised trial. California Collaborative Treatment Group. Lancet 1999; 354:891.
- Benson CA, Williams PL, Cohn DL, et al. Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial. The AIDS Clinical Trials Group 196/Terry Beirn Community Programs for Clinical Research on AIDS 009 Protocol Team. J Infect Dis 2000; 181:1289.
- Jacobson MA, French M. Altered natural history of AIDS-related opportunistic infections in the era of potent combination antiretroviral therapy. AIDS 1998; 12 Suppl A:S157.
- Kovacs JA, Masur H. Prophylaxis against opportunistic infections in patients with human immunodeficiency virus infection. N Engl J Med 2000; 342:1416.
- Dworkin M, Hanson D, Jones J, Kaplan J, Adult/Adolescent Spectrum of HIV Disease Project (ASD). The risk for Pneumocystis carinii pneumonia (PCP) and disseminated nontuberculous mycobacteriosis (dMb) after an antiretroviral therapy (ART) associated increase in the CD4+ T-lymphocyte count. In: Proceedings of the Sixth Conference on Retroviruses and Opportunistic Infections, Chicago, January 31-February 4, 1999:198. Abstract.
- Kirk O, Lundgren JD, Pedersen C, et al. Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy? AIDS 1999; 13:1647.
- Yangco BG, Von Bargen JC, Moorman AC, Holmberg SD. Discontinuation of chemoprophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection. HIV Outpatient Study (HOPS) Investigators. Ann Intern Med 2000; 132:201.
- Ledergerber B, Mocroft A, Reiss P, et al. It is safe to discontinue secondary prophylaxis for PCP in HIV-infected patients treated with HAART: results from eight prospective European cohorts. In: Proceedings of the Seventh Conference on Retroviruses and Opportunistic Infections, San Francisco, January 30-February 2, 2000:235. Abstract.
- Lederman MM, Connick E, Landay A, et al. Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315. J Infect Dis 1998; 178:70.
- El-Sadr WM, Burman WJ, Grant LB, et al. Discontinuation of prophylaxis for Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med 2000; 342:1085.
- Chaisson RE, Gallant JE, Keruly JC, Moore RD. Impact of opportunistic disease on survival in patients with HIV infection. AIDS 1998; 12:29.
- Benson CA, Williams PL, Currier JS, et al. A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome. Clin Infect Dis 2003; 37:1234.
- Ward TT, Rimland D, Kauffman C, et al. Randomized, open-label trial of azithromycin plus ethambutol vs. clarithromycin plus ethambutol as therapy for Mycobacterium avium complex bacteremia in patients with human immunodeficiency virus infection. Veterans Affairs HIV Research Consortium. Clin Infect Dis 1998; 27:1278.
- Dubé MP, Sattler FR, Torriani FJ, et al. A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group. J Infect Dis 1997; 176:1225.
- May T, Brel F, Beuscart C, et al. Comparison of combination therapy regimens for treatment of human immunodeficiency virus-infected patients with disseminated bacteremia due to Mycobacterium avium. ANRS Trial 033 Curavium Group. Agence Nationale de Recherche sur le Sida. Clin Infect Dis 1997; 25:621.
- Shafran SD, Singer J, Zarowny DP, et al. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group. N Engl J Med 1996; 335:377.
- Chaisson RE, Keiser P, Pierce M, et al. Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection. AIDS 1997; 11:311.
- Hafner R, Bethel J, Power M, et al. Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in human immunodeficiency virus-infected volunteers. Antimicrob Agents Chemother 1998; 42:631.
- Shafran SD, Singer J, Zarowny DP, et al. Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. Canadian HIV Trials Network Protocol 010 Study Group. J Infect Dis 1998; 177:252.
- Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR Morb Mortal Wkly Rep 2000; 49:185.
- Hsu O, Hill CJ, Kim M, et al. Decreased plasma efavirenz concentrations in a patient receiving rifabutin. Am J Health Syst Pharm 2010; 67:1611.
- Kirk O, Reiss P, Uberti-Foppa C, et al. Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy. Ann Intern Med 2002; 137:239.
- Shafran SD, Mashinter LD, Phillips P, et al. Successful discontinuation of therapy for disseminated Mycobacterium avium complex infection after effective antiretroviral therapy. Ann Intern Med 2002; 137:734.
- Aberg JA, Williams PL, Liu T, et al. A study of discontinuing maintenance therapy in human immunodeficiency virus-infected subjects with disseminated Mycobacterium avium complex: AIDS Clinical Trial Group 393 Study Team. J Infect Dis 2003; 187:1046.
- http://www.idsociety.org/Content.aspx?id=9088 (Accessed on December 12, 2011).
- Risk factors
- Host genetics
- CLINICAL MANIFESTATIONS
- Disseminated infection
- Localized disease
- Effect on HIV infection
- PREVENTION OF MAC DISEASE
- Clarithromycin versus placebo
- Azithromycin comparative trial
- Clarithromycin comparative trial
- Recommended drug choice
- Timing of the initiation of prophylaxis
- Discontinuation of prophylaxis
- General principles
- First-line agents
- Second-line agents
- Addition of third agent
- Addition of antiretroviral therapy
- Adjunctive therapy
- Monitoring of therapy
- Management of treatment failure
- Summary recommendations
- Safety of discontinuing MAC therapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS