Mycobacterium avium complex (MAC) is the most common systemic bacterial infection in subjects with advanced AIDS; it is characterized by fever, night sweats, weight loss or wasting, diarrhea, and abdominal pain, and is associated with a significant number of AIDS-related deaths.
Clinical trial results demonstrated that clarithomycin is effective in reducing the risk of developing disseminated MAC disease in subjects with advanced AIDS. In a randomized, double-blind, placebo-controlled study conducted in the United States and Europe, subjects with advanced AIDS (CD4 cell counts less than or equal to 100 cells) and a negative MAC blood culture received either clarithromycin 500 mg twice daily (n=341) or placebo twice daily (n=341). The median duration of treatment with clarithromycin was 10.6 months, as compared to a median duration of 8.2 months for the placebo-treated group. The risk of developing disseminated MAC was reduced by 69 percent in the clarithromycin-treated subject group, compared to placebo.
A statistically significant survival benefit was observed with clarithromycin. Mortality was reduced by 31%, 31%, and 20% at 6, 12, and 18 months, respectively. Since the analysis at 18 months includes subjects no longer receiving prophylaxis, the survival benefit of clarithomycin may be underestimated.
Disseminated MAC developed in 19 of the 341 patients receiving clarithromycin. Eleven of the patients developed strains of MAC which were resistant to clarithromycin. None of the 53 MAC isolates in the placebo group were resistant to clarithromycin.
The clarithromycin regimen was well tolerated by study participants. The only adverse event significantly more common among subjects treated with clarithromycin than placebo was taste perversion. Other adverse events occurring in 4% of more of the subjects taking clarithromycin include abdominal pain, diarrhea, and vomiting.
While only approximately 3% of HIV-positive subjects are diagnosed with disseminated MAC at the time of AIDS diagnosis, studies have shown that up to 40% of these subjects show clinical evidence of disseminated MAC within two years. In addition, MAC has been confirmed post-mortem in up to 50 % of patients with advanced AIDS.
Clarithromycin should not be used in pregnant women except in circumstances where no alternative therapy is appropriate. Calrithromycin should not be used in subjects receiving terfenadine who have pre-existing cardiac abnormalities or electrolyte disturbances.