EFFECT OF INTRAVENOUS IMMUNOGLOBULIN (IVIG) ON CD4-INFECTED CHILDREN IN A CLINICAL-TRIAL OF IVIG INFECTION PROPHYLAXIS( LYMPHOCYTE DECLINE IN HIV)

Our objective was to evaluate the effect of intravenous immunoglobulin (IVIG) on absolute CD4+ lymphocyte count (CD4+ count) trends in human immunodeficiency virus- (HIV) infected children enrolled in a trial o f IVIG for infection prophylaxis. To that end, we conducted a randomiz ed, double-blind, outpatient trial comparing subjects treated with 400 mg per kilogram of IVIG every 28 days with those given 0.1% albumin p lacebo. CD4+ counts were measured at entry and every 12 weeks. Twenty- eight clinical centers in mainland United States and Puerto Rico parti cipated. Previous reports showed IVIG efficacy for infection prophylax is in 313 patients with entry CD4+ counts of greater-than-or-equal-to 0.20 x 10(9)/L (greater-than-or-equal-to 200/mm3). Two hundred and sev enty-seven (89%) of these 313 children had three or more CD4+ counts m easured during the trial and were included in evaluation of CD4+ count trends. Rates of CD4+ count decline, as measured by regression slopes , were compared between IVIG and placebo groups using generalized line ar models, comparing unadjusted, age-adjusted, and standardized age-ad justed data. Potential covariate effects were assessed by modeling cha nge in CD4+ count in terms of log change between successive measuremen ts. Age-adjusted slope analysis showed slowing of CD4+ count decline b y 13.5 cells/mm3 per month in IVIG compared with placebo recipients (9 5% confidence interval, 3.1-23.9, p = 0.012). Modeling log change betw een measurements documented a beneficial effect of IVIG that was cumul ative over time and independent of other therapies. Occurrence of seri ous bacterial infection in the interval before CD4+ count measurement or death was independently associated with more rapid CD4+ count decli ne (p = 0.01 and p = 0.008, respectively). Zidovudine therapy was asso ciated with a transient increase in CD4+ count. Benefits of IVIG inclu de slowing of CD4+ count decline as well as previously reported reduct ions in serious and minor bacterial and viral infections in subjects w ith entry CD4+ counts of greater-than-or-equal-to 0.20 x 10(9)/L. This finding provides corroboration for the hypothesis that immunologic me chanisms contribute to the pathogenesis of CD4+ decline in HIV infecti on.