The development of rifabutin for prophylaxis against Mycobacterium avium complex infections

F. P. Siegal, Barbara Weiser, Harold Burger, K. Gehan, J. W M Gold, B. A. Wynne, S. D. Nightingale

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Rifabutin (formerly ansamycin), a semisynthetic derivative of rifamycin-S, has been in clinical use since 1982, initially as part of clinical efforts to treat disseminated infections with Mycobacterium avium complex (MAC) in the acquired immune deficiency syndrome (AIDS). Because of preliminary data suggesting a possible role as an antiretroviral agent, dose-related toxicities of the drug were explored in the mid-1980s. At high doses in patients with AIDS-related complex, a polyarthralgia syndrome developed, accompanied in some parts by uveitis. While having no useful activity in vivo against HIV-1, rifabutin appeared to prevent or delay the onset of clinically disseminated MAC infections in AIDS patients. These preliminary studies led to two identical prospective, placebo-controlled trials of rifabutin for the prevention of disseminated MAC infection, in which the principal endpoint was the reduction of MAC bacteraemia. Over 1100 subjects who had prior AIDS-defining opportunistic infections and ≤ 200 CD4 cells·mm-3 were randomized. Rifabutin use was associated with significant reduction in the frequency of MAC bacteraemia (60%), with concomitant reductions in symptoms related to MAC. Drug-related toxicity was minimal. These studies established the principal of MAC prophylaxis, as well as the safety and efficacy of rifabutin for the prevention of MAC infections in AIDS.

Original languageEnglish (US)
Pages (from-to)98-101
Number of pages4
JournalEuropean Respiratory Review
Volume5
Issue number25
StatePublished - 1995
Externally publishedYes

Keywords

  • Acquired immunodeficiency syndrome
  • Human immunodeficiency virus
  • Mycobacterial prophylaxis
  • Mycobacterium avium
  • Rifabutin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Siegal, F. P., Weiser, B., Burger, H., Gehan, K., Gold, J. W. M., Wynne, B. A., & Nightingale, S. D. (1995). The development of rifabutin for prophylaxis against Mycobacterium avium complex infections. European Respiratory Review, 5(25), 98-101.