ICL: MAC Prophylaxis and Treatment

ICL: MAC Prophylaxis and Treatment

Being Alive; November 1992
Walt Senterfitt

Three studies summarized the trials of Rifabutin (300 mg/day) for prophylaxis against MAC infections. Two large trials of people starting with CD4+ cell counts under 200 (and who were also taking an antiretroviral drug and PCP prophylaxis) both showed a reduction of incidence of new MAC infections of almost 50% in the people taking Rifabutin compared to those who got a placebo (11.4% vs 19.4% in one study and 9.1% vs. 16.0% in the other, over an 18-month period).

More than 40% of participants in both the drug and the placebo groups reported adverse events that could be considered side effects, without significantly more in the Rifabutin group. One study showed a small but statistically significant decrease in overall mortality during the study period for those on Rifabutin while the other study showed no difference in survival. In both studies, anyone who developed MAC was offered immediate treatment.

Comparable studies using clarithromycin, azithromycin, and other drugs as potential prophylactic agents have recently begun but do not yet have results.

Studies of various treatments were presented. The use of clarithromycin as single-agent treatment, presented by Dr. Richard Chaisson on Johns Hopkins, is fairly well known already. It compared three different dosage regimens of clarithromycin over 12 weeks of treatment for confirmed MAC: 500mg, 1000mg, or 2000mg each twice a day. All three doses were effective in eliminating MAC from the bloodstream by the end of 12 weeks, but the 2000mg dose did it in 27 days, the 100mg dose in 43 days, and the 500mg dose in 55 days. Adverse reactions (chiefly gastrointestinal upset) increased as the dose increased and required about 20% of the people to stop taking the drug.

The big problem is that resistance to the drug begins to develop at or soon after 12 weeks, in about 50% of those who take it. This resistance seems to happen regardless of which dose one is taking, and is clearly associated with the return of symptoms. All in all, it points to clarithromycin as a very valuable drug in treating MAC, but which needs to be used in combination with other drugs to prevent the development of resistance.

Various combination regimens of two to four anti-MAC drugs were represented by small studies. The drugs include, besides clarithromycin, azithromycin, ethambutol, rifampin, clofazimine, sparfloxacin, and liposome-encapsulated gentamycin. Nearly all the regimens are effective, and nearly all are intolerable to a significant number of people. What is needed are large enough trials of the most promising competing combinations to figure out the generally optimal regimens, as well as second and third choices for people who can't tolerate the first. In the meantime, most providers, at least in LA, are already using at least two and usually three drugs based on physician preference and assessment of an individual's likelihood of tolerating the particular combination.

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