PI Perspective #17

December 1995     View PDF     En español

Advances in Prevention and Treatment of MAC

Several new studies are now helping to optimize the prevention and treatment of MAC (mycobacterium avium complex), a serious infection common in advanced AIDS. Recent information suggests either clarithromycin or azithromycin alone, or in combination with rifabutin, may be more effective at preventing MAC than rifabutin alone. For treatment of MAC, new data show that a 3-drug combination using clarithromycin is superior to 2-drug or 4-drug combinations. These results will certainly define new standards of prevention and treatment for MAC.

The California Collaborative Treatment Group (CCTG) has provided Project Inform with preliminary results from their recent MAC prevention study. We would like to thank the CCTG for this information and applaud their decision to allow us to disseminate it prior to presentation at a scientific meeting. The study enrolled 693 people with fewer than 100 CD4+ cells, who received either azithromycin (1,200mg once a week), rifabutin (300mg daily) or the combination. The study suggests azithromycin is a good alternative, and possibly superior, to rifabutin in preventing MAC (an important consideration because of possible drug interactions) but the combination is better still. About 10% of people who developed MAC while receiving azithromycin developed resistance to both azithromycin and clarithromycin, and later could not use either drug for MAC treatment. Both drugs are similar and are considered to be the most potent therapies against MAC. Each should be used in combination with other anti-MAC drugs. People receiving azithromycin or rifabutin alone had similar side effects, while those receiving the combination had a slightly higher incidence of side effects. Another recent study showed that clarithromycin was also a good alternative to rifabutin.

A recent French study enrolled 132 people with MAC who received clarithromycin + clofazimine or clarithromycin + rifabutin + ethambutol. The doses used in this study were 450mg of rifabutin daily and 1,200mg daily of ethambutol. For the first two months the clarithromycin dosage was 2,000mg daily and the clofazimine dosage was 200mg daily; after two months both dosages were halved to 1,000mg daily, and 100mg daily respectively. People on the three drug combination were much less likely to develop resistance to clarithromycin, suggesting the combination will be effective longer. There was no difference shown between the two treatments in prolonging survival, decreasing fever or in clearing MAC from the blood. However this may be because the study may have been too small to clearly show such benefits.

A Canadian study enrolled 229 people with MAC who received a 3-drug combination (clarithromycin + rifabutin + ethambutol) or a 4-drug combination (ciprofloxacin + ethambutol + rifampin + clofazimine). The doses used were 1,000mg twice daily of clarithromycin, 600mg daily of rifabutin, 15mg/kg daily of ethambutol, 750mg twice daily of ciprofloxacin, 100mg of clofazimine daily and 600mg of rifampin daily. The rifabutin dosage was cut in half when almost half the people receiving the 600mg developed uveitis, a painful inflammation in the eye. People on the 3-drug combination were more likely to clear MAC from their blood than those on the 4-drug combination. Most importantly, people receiving the 3-drug combination survived longer than people receiving the 4-drug combination. Additionally, people using the 3-drug combination were more likely to clear MAC from their blood while receiving the original 600mg dose of rifabutin than those who received the lower dose, even though the higher dose was associated with serious eye inflammation.

A CCTG MAC treatment study enrolled 95 people with MAC who received clarithromycin + clofazimine or the two drugs plus ethambutol. The doses used were 2,000mg/day of clarithromycin, 100mg/day of clofazimine and 800mg/day of ethambutol. There was no difference between the two groups in clearing MAC from the blood, but the 3-drug combination may delay resistance to clarithromycin. The results of these studies show that a combination containing clarithromycin is probably the best treatment against MAC infection and that a 3-drug combination which includes clarithromycin may delay the emergence of clarithromycin resistant organisms.