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Previous Volume 335:384-391 August 8, 1996 Number 6 Next

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ABSTRACT

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.

Source Information

From Vanderbilt University, Nashville (M.P.); Abbott Laboratories, North Chicago, Ill. (S.C., D.H., G.N., JC.C.); the National Jewish Center for Immunology and Respiratory Medicine, Denver (L.H.); Therafirst Medical Center, Fort Lauderdale, Fla. (A.L.); Westchester County Medical Center (M.M.) and New York Medical College (G.P. W.), Valhalla, N.Y.; Heinrich Heine Universität, Düsseldorf, Germany (H.J.); Nalle Clinic, Charlotte, N.C. (J.J.); State University of New York Health Science Center, Syracuse (M.C.); and the Infectious Disease Research Institute, Tampa, Fla. (B.G.Y.).

Address reprint requests to Dr. Craft at Dept. 48V, Bldg. AP 34-3 South, Abbott Laboratories, 200 Abbott Park Rd., Abbott Park, IL 60064-3537.

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• Freedberg, K. A., Scharfstein, J. A., Seage III, G. R., Losina, E., Weinstein, M. C., Craven, D. E., Paltiel, A. D. (1998). The Cost-effectiveness of Preventing AIDS-Related Opportunistic Infections. JAMA 279: 130-136 [Abstract] [Full Text]  
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