Maternal and infant factors predicting disease progression in human immunodeficiency virus type 1-infected infants

Background. Infants with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection have widely variable courses. Previous studies sho wed that a number of maternal and infant factors, when analyzed separately, are associated with infant HIV-1 disease progression. In this study, clinc al, virologic, and immunologic characteristics in the mothers and infants w ere examined together to determine the predictors of disease progression by 18 months of age and the associations with rapid progression during the fi rst 6 months of life. Methods. One hundred twenty-two HIV-1-infected women whose infants were HIV -1 infected were identified from the Women and Infants Transmission Study ( WITS) cohort. WITS is a longitudinal natural history study of perinatal HIV -1 infection carried out in 6 sites in the continental United States and in Puerto Rico. The women were enrolled during pregnancy and their infants we re enrolled at the time of delivery and followed prospectively by a standar dized protocol. Virologic and immunologic studies were performed in laborat ories certified by National Institutes of Health-sponsored quality assuranc e programs. Maternal factors in pregnancy were used as potential predictors of infant disease progression (progression to Centers for Disease Control and Prevention [CDC] Clinical Class C disease or death by 18 months of age) or as correlates of progression at <6 months of age. Infant factors define d during the first 6 months of life were used as potential predictors of pr ogression during 6 to 18 months of age and as correlates of progression at <6 months of age. Results. Progression by 18 months of age occurred in 32% of infants and by 6 months of age in 15%. Maternal characteristics that, by univariate analysis, were significant pre dictors of infant disease progression by 18 months of age were elevated vir al load, depressed CD4(+)%, and depressed vitamin A. CD8(+)%, CD8(+) activa tion markers, zidovudine (ZDV) use, hard drug use, and gestational age at d elivery were not. When examined in a combined multivariate analysis of mate rnal characteristics, only vitamin A concentration independently predicted infant progression. Infant characteristics during the first 6 months of life that, by univariat e analysis, were associated with disease progression included elevated mean viral load at 1 to 6 months of age, depressed CD4(+)%, CDC Clinical Diseas e Category B, and growth delay. Early HIV-1 culture positivity (< 48 hours) , CD8(+)%, CD8(+) activation markers, and ZDV use during the first month of life did not predict progression. Multivariate analysis of infant characte ristics showed that the only independent predictors were progression to CDC Category B by 6 months of age (odds ratio [OR], 5.80) and mean viral load from 1 to 6 months of age (OR, 1.99). The final combined maternal and infant analysis included the significant ma ternal and infant characteristics in a multivariate analysis. It showed tha t factors independently predicting infant progression by 18 months of age w ere progression to CDC Category B by 6 months of age (OR, 5.80) and elevate d mean HIV-1 RNA copy number at 1 to 6 months of age (OR, 1.99). The characteristics associated with rapid progression to CDC Category C dis ease or death by 6 months of age were also examined. The only maternal char acteristic associated with progression by 6 months in multivariate analysis was low maternal CD4(+)%. The infant characteristics associated with progr ession by 6 months of age in multivariate analysis were depressed mean CD4( +)% from birth through 2 months and the presence of lymphadenopathy, hepato megaly, or splenomegaly by 3 months. Infant ZDV use was not assocciated wit h rapid progression. Conclusion. The strongest predictors of progression by 18 months are the pr esence of moderate clinical symptoms and elevated RNA copy number in the in fants in the first 6 months of life. In contrast, progression by 6 months i s associated with maternal and infant immune suppression, and the presence of infant clinical symptoms. The difference suggests that the key pathogene tic mechanisms responsible for progression may vary with age. These observa tions help provide direction for future pathogenesis research and assist in clinical care.