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Objective: To review the pathophysiology, epidemiology, treatment, and prophylaxis of disseminated Mycobacterium avium complex (MAC) infection in HIV-infected individuals., Data Sources: A MEDLINE (January 1966-July 1997) and AIDSLINE (January 1980-July 1997) search of basic science articles pertinent to the MAC infection in HIV-infected patients., Study Selection and Data Extraction: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion., Data Synthesis: The organism, epidemiology, and pathophysiology of disseminated MAC are discussed for background. A review of clinical trials for the treatment and prophylaxis of disseminated MAC are presented, along with unresolved issues concerning these topics., Conclusions: The incidence of disseminated MAC has increased dramatically with the AIDS epidemic. The infection can lead to increased morbidity and mortality in HIV-infected patients. Treatment regimens for patients with a positive culture for MAC from a sterile site should include two or more drugs, including clarithromycin. Prophylaxis against disseminated MAC should be considered for patients with a CD4 cell count of less than 50/mm3.

Pyrimethamine pharmacokinetics were studied in 11 human immunodeficiency virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Group Protocol 102). Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were determined after administration of the last dose. Noncompartmental and compartmental analyses were performed. Population pharmacokinetic analysis assuming a one-compartment model yielded the following estimates: area under the 24-h concentration-time curve, 42.7 +/- 12.3 micrograms.h/ml; halflife, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without HIV infection. Pyrimethamine pharmacokinetics did not differ significantly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimethamine levels and the incidence of adverse events. No significant differences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected patients that were similar to those in non-HIV-infected subjects and it did not alter the pharmacokinetics of zidovudine in these patients.