The drug rifabutin should be used to prevent Mycobacterium avium complex (MAC) in adults and adolescents with advanced HIV infection, reports a U.S. Public Health Service (PHS) Task Force on Prophylaxis and Therapy for MAC. If disseminated disease develops, the task force advises treatment with clarithromycin or azithromycin and at least one other agent. The full recommendations appear in the Sept. 16 issue of The New England Journal of Medicine.
The task force carefully considered the recommendations to assure that they best represent what is known about MAC. Considerable information about prophylaxis and therapy has emerged from studies during the last 12 to 24 months, much of which has not yet been published," says Henry Masur, M.D., chair of the task force and chief of the Critical Care Medicine Department of the Warren G. Magnuson Clinical Center, National Institutes of Health (NIH). "In formulating these recommendations, we hope to assist health care providers, and most importantly, benefit patients by providing a concise update of this rapidly evolving field." The PHS task force includes experts from government agencies, universities, private practice and the community.
MAC causes disseminated disease in up to 40 percent of HIV-infected individuals in the United States. Until the HIV epidemic, MAC was seldom associated with disease in humans.
The MAC organism is found widely in the environment and is thought to be acquired most commonly through the mouth or gastrointestinal tract. It can spread to the lungs, liver, spleen, lymph nodes, bone marrow, intestines and blood, causing chronic, debilitating symptoms -- persistent fever, night sweats, weight loss, fatigue, chronic diarrhea, abdominal pain, liver dysfunction and severe anemia.
According to the task force report, disseminated MAC can be most readily diagnosed by blood culture, which should be performed in patients with symptoms or laboratory abnormalities suggesting the disease.
To prevent MAC disease, the report suggests that patients with HIV infection and fewer than 100 CD4+ T cells receive 300 milligrams (mg.) per day of oral rifabutin for the rest of their lives, unless disseminated disease develops. In the latter case, a multiple drug treatment is needed. Patients must not have active MAC disease, M. tuberculosis or any other mycobacteria infection upon beginning prophylaxis. CD4+ T cells are immune system cells targeted and killed by HIV.
The 300 mg. dose of rifabutin is well-tolerated in patients. Some side effects have been reported including reduction in white blood cells and platelets, rashes and gastrointestinal disturbances, but these have been uncommon.
No other drug regimen is recommended currently to prevent MAC. Azithromycin and clarithromycin are promising agents for prophylaxis, but studies of these agents have not yet been completed.
Evidence is increasing that treatment for disseminated MAC can benefit patients, especially multiple drug regimens including either clarithromycin or azithromycin. Therefore, the task force suggests that all regimens, outside of a clinical trial, should consist of at least two drugs, including clarithromycin or azithromycin plus another agent.
According to the task force report, many physicians have added one or more of the following as second, third, or fourth agents: clofazimine, rifabutin, rifampin, ciprofloxacin and, in certain situations, amikacin. Isoniazid and pyrazinamide are not effective treatments for MAC. Continued therapy is recommended for the patient's lifetime, as long as clinical benefit and reduction of the mycobacteria are observed.
Diagnosis, prevention and therapy for children younger than 13 years with HIV infection follow guidelines similar to those for adults and adolescents.
On Dec. 23, 1992, the Food and Drug Administration (FDA) approved rifabutin as the first drug to prevent MAC disease in HIV-infected people with advanced disease. The FDA based the decision on clinical studies showing that patients who received rifabutin were one-third to one-half as likely to develop MAC as were patients who received placebo.
The PHS task force convened on Dec. 7 and 8, 1992. The Centers for Disease Control and Prevention (CDC) issued summary recommendations in the Morbidity and Mortality Weekly Report on June 25, 1993.
Members of the task force include: David L. Cohn, M.D., Denver Disease Control; Michael H. Cynamon, M.D., Veterans Affairs Medical Center; Lawrence R. Deyton, M.D., M.S.P.H., National Institute of Allergy and Infectious Diseases (NIAID), NIH; Robin J. Edison, M.D., FDA; Robert W. Elsinger, Ph.D., Office of AIDS Research, NIH; Jerrold J. Ellner, M.D., Case Western Reserve University; Judith Feinberg, M.D., Johns Hopkins University; Mark J. Goldberger, M.D., FDA; Charles Jeff Goodgame, M.D., private practice, Orlando, FL; Fred M. Gordin, M.D., Veterans Affairs Medical Center; Mark Harrington, Treatment Action Group; Diane V. Havik, M.D., University of California, San Diego; C. Robert Horsburgh, Jr., M.D., CDC; Clark B. Inderlied, Ph.D., Children's Hospital of Los Angeles; Carol A. Kemper, M.D., Stanford University School of Medicine; Joyce A. Korvick, M.D., NIAID, NIH; Linda L. Lewis, M.D., National Cancer Institute, NIH; Abe M. Macher, M.D., Health Resources and Services Administration; Henry Masur, M.D. (chair), NIH Clinical Center; Brent G. Petty, M.D., Johns Hopkins University; Michael A. Polis, M.D., M.P.H., NIAID, NIH; Fred Sattler, M.D., University of Southern California Medical Center, Elaine M. Stoand, M.D., National Heart Lung and Blood Institute, NIH; Richard J. Wallace, Jr., M.D., University of Texas Health Center at Tyler.
NIAID, one of 16 institutes at NIH, supports research on AIDS, tuberculosis, allergies, immunology and infectious diseases. NIH is an agency of the U.S. Public Health Service, part of the U.S. Department of Health and Human Services.