Am Fam Physician. 2000;61(4):1145
After approximately 15 years, Pneumocystis carinii pneumonia (PCP) remains one of the most serious threats to patients with human immunodeficiency virus 1 (HIV-1) who live in the more developed countries. The available prophylactic regimens based on co-trimoxazole, dapsone alone or in combination with pyrimethamine, atovaquone and aerosolized pentamidine are effective, but intolerance is common in up to 50 percent of patients with HIV-1 infection. In a double-blind randomized trial of patients with HIV-1 infection and CD4 cell counts less that 100 per mm3 (100 × 106 per L), a weekly dosage of azithromycin alone or in combination with rifabutin proved more effective than rifabutin alone for prophylactic treatment of disseminated Mycobacterium avium disease. From this study, Dunne and colleagues assessed the additional clinical effectiveness of azithromycin-containing regimens as prophylaxis for PCP compared with a regimen of rifabutin alone.
Patients attending the 13 participating centers who met study criteria were randomly assigned to one of three treatment groups. Of the 693 patients in the study, 233 received azithromycin in a dosage of 1,200 mg weekly, 236 patients received rifabutin in a dosage of 300 mg daily and 224 patients received the two agents in combination. All patients were assessed on a monthly basis during the follow-up period.
During the follow-up period, 85 episodes of PCP were documented in 78 patients. The rate of PCP occurrence per 100 patient years was 25 for rifabutin, 12 for azithromycin and 13 for the combination of drugs. Significantly more patients remained free of PCP in the azithromycin-treated groups than in the group receiving rifabutin alone. The authors estimate that patients who received azithromycin alone or in combination had a 45 percent lower risk of developing PCP than patients who received rifabutin alone. The protective effect was strongest in patients without a previous history of PCP. This appeared to be the only variable that influenced the study outcome. Analyses to account for age, sex, race, baseline CD4 cell count, and biochemical markers at baseline showed no impact on the prophylactic treatment or development of PCP. Although a high proportion of patients reported side effects (90 percent for combination therapy, 88 percent for azithromycin therapy and 76 percent for rifabutin therapy), these were mostly mild gastrointestinal upsets that occurred in patients on the azithromycin-containing regimens. Discontinuation because of drug-related side effects occurred in 16 percent of rifabutin-treated patients, 14 percent of the azithromycin-only–treated patients and 23 percent of the patients who received combination therapy.
The authors conclude that weekly azithromycin-based regimens provide effective primary prophylaxis against PCP in patients with HIV-1 infection. The ease of weekly administration and lack of known interaction with agents used in multidrug antiretroviral regimens makes azithromycin an attractive addition to prophylactic regimens.