Two Controlled Trials of Rifabutin Prophylaxis against Mycobacterium avium Complex Infection in AIDS

Stephen D. Nightingale, D. William Cameron, Fred M. Gordin, Paul M. Sullam, David L. Cohn, Richard E. Chaisson, Lawrence J. Eron, Paula D. Sparti, Bernard Bihari, David L. Kaufman, John J. Stern, Daniel D. Pearce, Winkler G. Weinberg, Anthony Lamarca, Frederick P. Siegal

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383 Scopus citations

Abstract

Disseminated Mycobacterium avium complex infection eventually develops in most patients with the acquired immunodeficiency syndrome (AIDS). This infection results in substantial morbidity and reduces survival by about six months. We conducted two randomized, double-blind, multicenter trials of daily prophylactic treatment with either rifabutin (300 mg) or placebo. All the patients had AIDS and CD4 cell counts ≤ 200 per cubic millimeter. The primary end point was M. avium complex bacteremia as assessed monthly by blood culture. The secondary end points were signs and symptoms associated with disseminated M. avium complex infection, adverse events, hospitalization, and survival. In the first trial, M. avium complex bacteremia developed in 51 of 298 patients (17 percent) assigned to placebo and 24 of 292 patients (8 percent) assigned to rifabutin (P<0.001). In the second trial, bacteremia developed in 51 of 282 patients in the placebo group (18 percent) and 24 of 274 patients in the rifabutin group (9 percent) (P = 0.002). Rifabutin significantly delayed fatigue, fever, decline in the Karnofsky performance score (by ≤ 20 percent), decline in the hemoglobin level (by more than 10 percent), elevation in alkaline phosphatase, and hospitalization. The incidence of adverse events was similar with rifabutin and placebo. Overall survival did not differ significantly between the two groups, although there were fewer deaths with rifabutin (33) than with placebo (47) during the double-blind phase (P = 0.086). The distribution of minimal inhibitory concentrations of rifabutin among the isolates of M. avium complex did not differ significantly between the treatment groups. Rifabutin, given prophylactically, reduces the frequency of disseminated M. avium complex infection in patients with AIDS and CD4 counts ≤ 200 per cubic millimeter., Mycobacterium avium complex was among the first opportunistic pathogens identified in patients with the acquired immunodeficiency syndrome (AIDS)1. Since 1987, the prevalence of this infection among such patients has steadily increased. This increase has coincided with the introduction of antiretroviral and prophylactic therapies that have delayed the onset of AIDS-defining events and prolonged survival2. At present, the prevalence of M. avium complex bacteremia is approximately 5 percent at the time of the diagnosis of AIDS, and it increases by approximately 20 percent per year3. The incidence of M. avium complex is unrelated to age, sex, race, or…

Original languageEnglish
Pages (from-to)828-833
Number of pages6
JournalNew England Journal of Medicine
Volume329
Issue number12
DOIs
StatePublished - 16 Sep 1993
Externally publishedYes

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