2 CONTROLLED TRIALS OF RIFABUTIN PROPHYLAXIS AGAINST MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN AIDS

Background. Disseminated Mycobacterium avium complex infection eventua lly develops in most patients with the acquired immunodeficiency syndr ome (AIDS). This infection results in substantial morbidity and reduce s survival by about six months. Methods. 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 CD 4 cell counts less-than-or-equal-to 200 per cubic millimeter. The prim ary end point was M. avium complex bacteremia as assessed monthly by b lood culture. The secondary end points were signs and symptoms associa ted with disseminated M. avium complex infection, adverse events, hosp italization, and survival. Results. In the first trial, M. avium compl ex 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 rifab utin group (9 percent) (P = 0.002). Rifabutin significantly delayed fa tigue, fever, decline in the Karnofsky performance score (by greater-t han-or-equal-to 20 percent), decline in the hemoglobin level (by more than 10 percent), elevation in alkaline phosphatase, and hospitalizati on. The incidence of adverse events was similar with rifabutin and pla cebo. Overall survival did not differ significantly between the two gr oups, although there were fewer deaths with rifabutin (33) than with p lacebo (47) during the double-blind phase (P = 0.086). The distributio n of minimal inhibitory concentrations of rifabutin among the isolates of M. avium complex did not differ significantly between the treatmen t groups. Conclusions. Rifabutin, given prophylactically, reduces the frequency of disseminated M. avium complex infection in patients with AIDS and CD4 counts less-than-or-equal-to 200 per cubic millimeter.