A RANDOMIZED TRIAL OF CLARITHROMYCIN AS PROPHYLAXIS AGAINST DISSEMINATED MYCOBACTERIUM-AVIUM COMPLEX 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 stag es of the acquired immunodeficiency syndrome (AIDS). We studied the ef ficacy and safety of prophylactic treatment with clarithromycin, a mac rolide antibiotic. Methods We conducted a randomized, placebo-controll ed, 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 perform ance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, an d a life expectancy of at least six months. Results After the first in terim analysis, the study was stopped. M. avium complex infection deve loped in 19 of the 333 patients (6 percent) assigned to clarith romyci n and in 53 of the 334 (16 percent) assigned to placebo (adjusted haza rd 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 pa tients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromyc in group, isolates from 11 of the 19 patients with M. avium complex in fection were resistant to clarithromycin. Prophylaxis with clarithromy cin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo grou p, P<0.001) and rectal disorders (8 percent vs. 3 percent, P=0.007); h owever, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively). Conclusions In pa tients with advanced AIDS, the prophylactic administration of clarithr omycin is well tolerated, prevents M. avium complex infection, and red uces mortality. (C) 1966, Massachusetts Medical Society.