A Randomized Trial of Clarithromycin as Prophylaxis against DisseminatedMycobacterium aviumComplex Infection in Patients with Advanced Acquired Immunodeficiency Syndrome

BACKGROUND: Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic. METHODS: We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months. RESULTS: After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively). CONCLUSIONS: In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.