Prophylaxis against Disseminated Mycobacterium avium Complex with Weekly Azithromycin, Daily Rifabutin, or Both
Diane V. Havlir, M.D., Michael P. Dubé, M.D., Fred R. Sattler, M.D., Donald N. Forthal, M.D., Carol A. Kemper, M.D., Michael W. Dunne, M.D., David M. Parenti, M.D., James P. Lavelle, M.D., A. Clinton White, M.D., Mallory D. Witt, M.D., Samuel A. Bozzette, M.D., Ph.D., J. Allen McCutchan, M.D., for The California Collaborative Treatment Group
Background Azithromycin is active in treating Mycobacteriumavium complex disease, but it has not been evaluated as primaryprophylaxis in patients with human immunodeficiency virus (HIV)infection. Because the drug is concentrated in macrophages andhas a long half-life in tissue, there is a rationale for once-weeklydosing.
Methods We compared three prophylactic regimens in a multicenter,double-blind, randomized trial involving 693 HIV-infected patientswith fewer than 100 CD4 cells per cubic millimeter. The patientswere assigned to receive rifabutin (300 mg daily), azithromycin(1200 mg weekly), or both drugs. They were monitored monthlywith blood cultures for M. avium complex.
Results In an intention-to-treat analysis, the incidence ofdisseminated M. avium complex infection at one year was 15.3percent with rifabutin, 7.6 percent with azithromycin, and 2.8percent with both drugs. The risk of the infection in the azithromycingroup was half that in the rifabutin group (hazard ratio, 0.53;P = 0.008). The risk was even lower when two-drug prophylaxiswas compared with rifabutin alone (hazard ratio, 0.28; P<0.001)or azithromycin alone (hazard ratio, 0.53; P = 0.03). Amongthe patients in whom azithromycin prophylaxis was not successful,11 percent of M. avium complex isolates were resistant to azithromycin.Dose-limiting toxic effects were more common with the two-drugcombination than with azithromycin alone (hazard ratio, 1.67;P = 0.03). Survival was similar in all three groups.
Conclusions For protection against disseminated M. avium complexinfection, once-weekly azithromycin is more effective than dailyrifabutin and infrequently selects for resistant isolates. Rifabutinplus azithromycin is even more effective but is not as welltolerated.
Source Information
From the University of California, San Diego, and the Veterans Affairs Medical Center, La Jolla, Calif. (D.V.H., S.A.B., J.A.M.); the University of Southern California, Los Angeles (M.P.D., F.R.S.); the University of California, Irvine (D.N.F.); Santa Clara Valley Medical Center, San Jose, Calif. (C.A.K.); Pfizer Central Research, Groton, Conn. (M.W.D.); George Washington University, Washington, D.C. (D.M.P.); Georgetown University, Washington, D.C. (J.P.L.); Baylor College of Medicine, Houston (A.C.W.); Harbor–UCLA Medical Center, Torrance, Calif. (M.D.W.); and the RAND Health Science Program, Santa Monica, Calif. (S.A.B.). Other authors who contributed to this study were Stephen D. Nightingale, M.D. (University of Texas Southwestern Medical Center, Dallas); Kent A. Sepkowitz, M.D. (New York Hospital–Cornell Medical Center, New York); Rob Roy MacGregor, M.D. (University of Pennsylvania, Philadelphia); Sarah H. Cheeseman, M.D. (University of Massachusetts, Worcester); Francesca J. Torriani, M.D. (University of California, San Diego); Michael T. Zelasky, M.S., Debra J. Williams, M.D., Ph.D., and Scott J. Hopkins, M.D. (Pfizer Central Research, Groton, Conn.); and Princy N. Kumar, M.D. (Georgetown University, Washington, D.C.).Presented in part at the Third Conference on Retroviruses and Opportunistic Infections, Washington, D.C., January 28–February 1, 1996.
Address reprint requests to Dr. Havlir at the UCSD Treatment Center, University of California, San Diego, 2760 Fifth Ave., Suite 300, San Diego, CA 92103.
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