Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count - A randomized, double-blind, placebo-controlled trial

Background: Patients infected with HIV who experience increases in CD4(+) c ell counts are at reduced risk for opportunistic infections. However, the s afety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain. Objective: To compare the rate of M. avium complex infection in patients wi th increased CD4(+) cell counts who receive azithromycin and those receivin g placebo. Design: Randomized, double-blind, placebo-controlled trial. Setting: 29 university-based clinical centers in the United States. Participants: 643 HIV-1-infected patients with a previous CD4(+) cell count less than 0.05 x 10(9) cells/L and a sustained increase to greater than 0. 10 x 10(9) cells/L during antiretroviral therapy. Intervention: Azithromycin, 1200 mg once weekly (n = 321), or matching plac ebo (n = 322). Measurements: Mycobacterium avium complex cultures, CD4+ cell counts, and c linical evaluations for AIDS-defining illnesses and bacterial infections we re done every 8 weeks. Plasma HIV-1 RNA levels were measured at 16-week int ervals. Results: During follow-up (median, 16 months), 2 cases of M. avium complex infection were reported among the 321 patients assigned to placebo (inciden ce rate, 0.5 event per 100 person-years [95% CI, 0.06 to 1.83 events per 10 0 person-years]) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a tr eatment difference of 0.5 event per 100 person-years (CI, -0.20 to 1.21 eve nts per 100 person-years) for placebo versus azithromycin. Both cases were atypical in that M. avium complex was localized to the vertebral spine. Pat ients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]). Conclusions: Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4(+) cell count while receiving antiretroviral therapy.