Rifabutin for the Prevention of Mycobacterium avium Complex Bacteraemia in AIDS and HIV-Positive Patients with CD4 Counts ≤ 200 Cells/μl

Abstract

In an open-label, nonrandomised, noncomparative treatment investigational new drug (IND) study, 536 patients with either the acquired immunodeficiency syndrome (AIDS) or positive human immunodeficiency virus (HIV) serology and low CD4 counts were administered rifabutin 300 mg/day prophylactically in an attempt to prevent or delay the development of Mycobacterium avium complex (MAC) bacteraemia. The purpose of the study was to allow HIV-positive and AIDS patients wider access to rifabutin for MAC prophylaxis while the application for marketing approval was under review. Patients included in the study had either a diagnosis of AIDS and a CD4 count of ≤ 200 cells/µl or were HIV-positive with a CD4 count of ≤ 100 cells/µl (but without an AIDS-defining event). Patients eligible for inclusion were to have no evidence of disseminated MAC disease as evaluated by a blood culture taken within 21 days before treatment. 19 of 533 evaluable patients (3.6%) with negative baseline cultures developed MAC bacteraemia. In addition, MAC was isolated from the sputum of 1 other patient. Fever, night sweats, diarrhoea and abdominal pain remained absent in 57 to 71% of patients. CD4 counts and Karnofsky scores generally remained stable or improved in more than 80% of patients. The most common adverse events (those with a frequency > 1%) attributable to rifabutin were leucopenia (7.1%), rash (5.2%), nausea and diarrhoea (4.1% each), headache (3.0%) and abdominal pain (2.2%). The results of this study, within the limitations of the study design, are consistent with the findings of phase III placebo-controlled clinical trials showing that rifabutin prevents or delays MAC bacteraemia in HIV-positive or AIDS patients with low CD4 counts. Rifabutin appears to be well tolerated with a relatively low incidence of (mostly minor) adverse events.