Comparison of atovaquone and azithromycin with trimethoprim-sulfamethoxazole for the prevention of serious bacterial infections in children with HIV infection

Background. Trimethoprim- sulfamethoxazole ( TMP- SMZ) has been used extensively for the prevention of Pneumocystis carinii ( also referred to as Pneumocystis jiroveci) pneumonia ( PCP) and other opportunistic infections in human immunodeficiency virus ( HIV) - infected children. Because the efficacy of TMP- SMZ for treatment of bacterial infections is limited, it is sometimes poorly tolerated, and there is risk of emergence of drug- resistant strains associated with widespread use, we evaluated a regimen that included atovaquone and azithromycin. Methods. A randomized, double- blind, placebo- controlled trial was designed to determine whether atova-quone-azithromycin had equivalent efficacy to TMP- SMZ for the prevention of serious bacterial infections and to compare the long- term tolerance, PCP breakthrough rates, and nonserious bacterial infection rates among HIVinfected children aged 3 months to 19 years. Children qualified for PCP prophylaxis ( on the basis of Centers for Disease Control and Prevention recommendations) were randomized to receive atovaquone- azithromycin or TMP-SMZ daily for greater than or equal to 2 years. Results. Data from 366 of the 369 eligible patients ( median duration of follow- up, 3 years) showed that the estimated rates of serious bacterial infection - related events were lower among atovaquone- azithromycin recipients than among TMP- SMZ recipients ( 17.3 vs. 24.2 events per 100 patient- years; difference, 6.9 events per 100 patientyears; 95% confidence interval [ CI], - 0.22 to 14.12). Rates for all end points ( serious bacterial infection, PCP, Mycobacterium avium complex infection, and serious and nonserious bacterial infection - related deaths) were 19.7 and 27.7 events per 100 patient- years, respectively ( difference, 7.9 events per 100 patient- years; 95% CI, - 0.28 to 15.54 events per 100 patient- years). The results marginally favored atovaquone- azithromycin therapy statistically. Atovaquone- azithromycin and TMP- SMZ therapies had similar adverse event profiles. Conclusions. We conclude that, in HIV- infected children, atovaquone- azithromycin is as effective as TMPSMZ for the prevention of serious bacterial infections and is similarly tolerated.