CONTROLLED TRIAL OF INTRAVENOUS IMMUNE GLOBULIN FOR THE PREVENTION OFSERIOUS BACTERIAL-INFECTIONS IN CHILDREN RECEIVING ZIDOVUDINE FOR ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Background. Serious bacterial infections are common in children infect ed with the human immunodeficiency virus (HIV). Studies performed befo re zidovudine became standard therapy found that intravenous immune gl obulin decreases the number of serious bacterial infections in these c hildren. We designed a multicenter study to evaluate the efficacy of i ntravenous immune globulin in children with advanced HIV infection who were receiving zidovudine. Methods. In a double-blind trial 255 child ren between 3 months and 12 years of age who had the acquired immunode ficiency syndrome (AIDS) or AIDS-related complex were randomly assigne d to receive either intravenous immune globulin (400 mg per kilogram o f body weight) (n = 129) or placebo (0.1 percent albumin) (n = 126) ev ery 28 days. All children received 180 mg of zidovudine per square met er of body-surface area orally four times daily. Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim -sulfamethoxazole. The median length of follow-up was 30.6 months. Res ults. The estimated two-year rates of serious bacterial infections wit h confirmed pathogens were 16.9 percent for the immune globulin group and 24.3 percent for the placebo group (relative risk, 0.60; 95 percen t confidence interval, 0.35 to 1.04; P = 0.07). The treatment effect w as seen primarily among the 174 children who were not receiving trimet hoprim-sulfamethoxazole prophylaxis at entry; the estimated two-year r ates of infection were 11.3 percent for the immune globulin group and 26.8 percent for the placebo group (relative risk, 0.45; 95 percent co nfidence interval, 0.22 to 0.91; P = 0.03). For the 81 children who we re receiving trimethoprim-sulfamethoxatele prophylaxis initially, the rates were 27.7 percent in the immune globulin group and 17.7 percent in the placebo group (relative risk, 1.26; 95 percent confidence inter val, 0.44 to 3.66; P = 0.67). The two-year survival was similar in the two groups: 79.2 percent among immune globulin recipients and 75.4 pe rcent among placebo recipients (P = 0.41). Conclusions. In children wi th advanced HIV disease who are receiving zidovudine, intravenous immu ne globulin decreases the risk of serious bacterial infections. Howeve r, this benefit is apparent only in children who are not receiving tri methoprim-sulfamethoxazole as prophylaxis.