Discontinuation of prophylaxis against Mycobacterium avium complex diseasein HIV-infected patients who have a response to antiretroviral therapy.

Background: Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV ) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantial ly with antiviral therapy. Methods: We conducted a multicenter, double-blind, randomized trial of trea tment with azithromycin (1200 mg weekly) as compared with placebo in HIV-in fected patients whose CD4+ cell counts had increased from less than 50 to m ore than 100 per cubic millimeter in response to antiretroviral therapy. Th e primary end point was M. avium complex disease or bacterial pneumonia. Results: A total of 520 patients entered the study; the median CD4+ cell co unt at entry was 230 per cubic millimeter. In 48 percent of the patients, t he HIV RNA value was below the level of quantification. The median prior na dir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the pati ents had had an acquired immunodeficiency syndrome-defining illness. During follow-up over a median period of 12 months, there were no episodes of con firmed M. avium complex disease in either group (95 percent confidence inte rval for the rate of disease in each group, 0 to 1.5 episodes per 100 perso n-years). Three patients in the azithromycin group (1.2 percent) and five i n the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50 ; P=0.48). Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups. Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azith romycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; re lative risk, 6.6; P=0.002). Conclusions: Azithromycin prophylaxis can safely be withheld in HIV-infecte d patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy. (N Engl J Med 2000 ;342:1085-92.) (C) 2000, Massachusetts Medical Society.