title: Effect of intravenous immunoglobulin (IVIG) on CD4+ lymphocyte decline in HIV-infected children in a clinical trial of IVIG infection prophylaxis. The National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.
abstract: 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 of IVIG for infection prophylaxis. To that end, we conducted a randomized, double-blind, outpatient trial comparing subjects treated with 400 mg per kilogram of IVIG every 28 days with those given 0.1% albumin placebo. CD4+ counts were measured at entry and every 12 weeks. Twenty-eight clinical centers in mainland United States and Puerto Rico participated. Previous reports showed IVIG efficacy for infection prophylaxis in 313 patients with entry CD4+ counts of > or = 0.20 x 10(9)/L (> or = 200/mm3). Two hundred and seventy-seven (89%) of these 313 children had three or more CD4+ counts measured 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 linear models, comparing unadjusted, age-adjusted, and standardized age-adjusted data. Potential covariate effects were assessed by modeling change in CD4+ count in terms of log change between successive measurements. Age-adjusted slope analysis showed slowing of CD4+ count decline by 13.5 cells/mm3 per month in IVIG compared with placebo recipients (95% confidence interval, 3.1-23.9, p = 0.012). Modeling log change between measurements documented a beneficial effect of IVIG that was cumulative over time and independent of other therapies. Occurrence of serious bacterial infection in the interval before CD4+ count measurement or death was independently associated with more rapid CD4+ count decline (p = 0.01 and p = 0.008, respectively). Zidovudine therapy was associated with a transient increase in CD4+ count. Benefits of IVIG include slowing of CD4+ count decline as well as previously reported reductions in serious and minor bacterial and viral infections in subjects with entry CD4+ counts of > or = 0.20 x 10(9)/L. This finding provides corroboration for the hypothesis that immunologic mechanisms contribute to the pathogenesis of CD4+ decline in HIV infection.
authors.affiliation: Adolescent and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: L M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: J
authors.initials: J
authors.lastname: Bethel
authors.forename: J
authors.initials: J
authors.lastname: Moye
authors.forename: P
authors.initials: P
authors.lastname: Flyer
authors.forename: R
authors.initials: R
authors.lastname: Nugent
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007223:Infant; D007958:Leukocyte Count; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D012044:Regression Analysis; D013997:Time Factors; D016896:Treatment Outcome; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D016756:Immunoglobulins, Intravenous; D015215:Zidovudine