I. Two different species of non-tuberculous mycobacteria
II. Disseminated form
- Usually occurs in pts with CD4 < 100
- Causes constitutional sx, weight loss, and diarrhea
- Associated with reduced survival in PWA's
- Environmental measures may have role as pts don't acquire MAC until AIDS is advanced
- 2 multicenter randomized double-blind trials compared rifabutin 300mg QD with placebo. (NEJM 329:828, 1993)
- 1100 pts with AIDS and CD4 <200; avg. treatment duration 6.5 mos.
- Rifabutin group had 8% MAC bacteremia vs 17% for placebo (sig.)
- Also statistically sig. reduction in sx and hosps with rifabutin
- Nonsignificant trend toward fewer deaths with rifabutin (33 vs 47; p= 0.086)
- Concerns include adverse reactions (neutropenia, thrombocytopenia, GI disturbances); increased use leading to increase in rifabutin-resistant M. tuberculosis, and interactions with other drugs (e.g. increases hepatic metabolism of AZT)
- NEJM 335:384, 1996-JW
- 667 pts with AIDS and CD4 < 100 randomized to clarithromycin vs. placebo (dose?)
- RR of MAC bacteremia over 14 mos. f/u was 0.36 with clarithromycin
- Azithromycin 1200mg/wk vs. rifabutin 300mg/d vs both (NEJM 335:392, 1996-JW)
- RR of developing MAC bacteremia was 0.50 with azithromycin compared with rifabutin
- RR of developing MAC bacteremia was 0.50 with both compared with azithromycin alone
- Combination therapy conferred no survival advantage (how long f/u?) and ass'd with 90% rate of adverse events
- USPHS task force report recommended rifabutin prophylaxis for HIV-infected pts with CD4 < 100 (NEJM, 329:832?, 1993); CDC recommends only when CD4 < 75 (MMWR 44:1, 1995)
- However, if CD4 counts start to rise with antiretroviral therapy, probably OK to stop (520 pts with CD4 counts rising to > 100 on antiretrovirals randomized to weekly axithromycin vs. placebo; over median 12mo f/u, no diff. in incidence of MAC infections or mortality (NEJM 342:1085, 2000--JW)
- Treatment: many drugs used, but not a lot of comparative data.
- Drugs in use include clarithromycin, azithromycin, rifampin, rifabutin, clofazimine, ethambutol, ciprofloxacin, amikacin; also 2 new drugs are being evaluated: levofloxacin and roxithromycin.