Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both

Diane V. Havlir, Michael P. Dubé, Fred R. Sattler, Donald N. Forthal, Carol A. Kemper, Michael W. Dunne, David M. Parenti, James P. Lavelle, A. Clinton White, Mallory D. Witt, Samuel A. Bozzette, J. Allen Mccutchan

Research output: Contribution to journalArticle

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Abstract

Background: Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing. Methods: We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV- infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They were monitored monthly with blood cultures for M. avium complex. Results: In an intention-to-treat analysis, the incidence of disseminated M. avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, 0.53; P=0.008). The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, 0.28; P<0.001) or azithromycin alone (hazard ratio, 0.53; P=0.03). Among the 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-drug combination 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 complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates. Rifabutin plus azithromycin is even more effective but is not as well tolerated.

Original languageEnglish
Pages (from-to)392-398
Number of pages7
JournalNew England Journal of Medicine
Volume335
Issue number6
DOIs
StatePublished - Aug 8 1996
Externally publishedYes

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Rifabutin
Mycobacterium avium Complex
Azithromycin
Pharmaceutical Preparations
Infection
HIV
Intention to Treat Analysis
Poisons
Virus Diseases
Drug Combinations
Half-Life
Macrophages

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Havlir, D. V., Dubé, M. P., Sattler, F. R., Forthal, D. N., Kemper, C. A., Dunne, M. W., ... Mccutchan, J. A. (1996). Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. New England Journal of Medicine, 335(6), 392-398. https://doi.org/10.1056/NEJM199608083350604

Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. / Havlir, Diane V.; Dubé, Michael P.; Sattler, Fred R.; Forthal, Donald N.; Kemper, Carol A.; Dunne, Michael W.; Parenti, David M.; Lavelle, James P.; White, A. Clinton; Witt, Mallory D.; Bozzette, Samuel A.; Mccutchan, J. Allen.

In: New England Journal of Medicine, Vol. 335, No. 6, 08.08.1996, p. 392-398.

Research output: Contribution to journalArticle

Havlir, DV, Dubé, MP, Sattler, FR, Forthal, DN, Kemper, CA, Dunne, MW, Parenti, DM, Lavelle, JP, White, AC, Witt, MD, Bozzette, SA & Mccutchan, JA 1996, 'Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both', New England Journal of Medicine, vol. 335, no. 6, pp. 392-398. https://doi.org/10.1056/NEJM199608083350604
Havlir, Diane V. ; Dubé, Michael P. ; Sattler, Fred R. ; Forthal, Donald N. ; Kemper, Carol A. ; Dunne, Michael W. ; Parenti, David M. ; Lavelle, James P. ; White, A. Clinton ; Witt, Mallory D. ; Bozzette, Samuel A. ; Mccutchan, J. Allen. / Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. In: New England Journal of Medicine. 1996 ; Vol. 335, No. 6. pp. 392-398.
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AU - Havlir, Diane V.

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AU - Forthal, Donald N.

AU - Kemper, Carol A.

AU - Dunne, Michael W.

AU - Parenti, David M.

AU - Lavelle, James P.

AU - White, A. Clinton

AU - Witt, Mallory D.

AU - Bozzette, Samuel A.

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