Background: Macrolides have been reported to be effective for the prevention of cryptosporidiosis in persons with HIV infection.
Objective: To evaluate the efficacy of clarithromycin and rifabutin for the prevention of cryptosporidiosis in persons with advanced HIV infection.
Design: Cross-protocol analysis involving 2288 individuals with a history of a CD4 cell counts of ≤ 100 × 106 cell/l who were enrolled in two prospective clinical trials to prevent Mycobacterium avium complex (MAC) infection and cytomegalovirus (CMV) end-organ disease.
Interventions: Clarithromycin 500 mg twice daily, rifabutin 300–450 mg daily, the combination of the two or no MAC prophylaxis.
Main outcome measurement: Laboratory-confirmed cryptosporidiosis. Subjects were analyzed in an intent-to-treat and as-treated manner using time-to-event analyses (Cox proportional hazards models).
Results: The median length of follow up was 463 days. The median CD4 count at entry was 29 × 106 cell/l (range 0–182). There were 60 cases of cryptosporidiosis during the prospective observational period, with an event rate of 2.2 per 100 person-years. In the intent-to-treat [relative risk (RR) 0.50; 95% confidence interval (CI) 0.26–0.96;P = 0.04] and as-treated (RR 0.42; 95% CI 0.20–0.91;P = 0.03) analyses, rifabutin alone was significantly associated with a lower rate of cryptosporidiosis. Clarithromycin alone was not protective in similar analyses (P = 0.98 and 0.90, respectively).
Conclusions: In doses used to prevent MAC infection, rifabutin but not clarithromycin decreases the risk of developing cryptosporidiosis in persons with advanced HIV infection who are not receiving potent combination antiretroviral therapy.