PEDIATRICS Vol. 105 No. 1 January 2000, p. e8

ELECTRONIC ARTICLE:
Maternal and Infant Factors Predicting Disease Progression in Human Immunodeficiency Virus Type 1-Infected Infants

Received Feb 16, 1999; accepted Aug 13, 1999.

Kenneth C. Rich^*, Mary G. Fowler, Lynne M. Mofenson^§, Rasha Abboud, Jane Pitt^¶, Clemente Diaz^#, I. Celine Hanson^**, Ellen Cooper, Hermann Mendez^§§, and for the Women and Infants Transmission Study Group

From the ^* Department of Pediatrics, University of Illinois at Chicago, Illinois;  National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; ^§ National Institute of Child Health and Human Development, Bethesda, Maryland;  New England Research Institutes, Watertown, Massachusetts; ^¶ Columbia University College of Physicians and Surgeons, New York, New York; ^# University of Puerto Rico, San Juan, Puerto Rico; ^** Baylor College of Medicine, Houston, Texas;  Boston City Hospital, Boston, Massachusetts; and ^§§ State University of New York Health Science Center, Brooklyn, New York.

Background.  Infants with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection have widely variable courses. Previous studies showed that a number of maternal and infant factors, when analyzed separately, are associated with infant HIV-1 disease progression. In this study, clincal, virologic, and immunologic characteristics in the mothers and infants were examined together to determine the predictors of disease progression by 18 months of age and the associations with rapid progression during the first 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 were enrolled at the time of delivery and followed prospectively by a standardized protocol. Virologic and immunologic studies were performed in laboratories certified by National Institutes of Health-sponsored quality assurance 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 defined during the first 6 months of life were used as potential predictors of progression 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 predictors of infant disease progression by 18 months of age were elevated viral load, depressed CD4⁺%, and depressed vitamin A. CD8⁺%, CD8⁺ activation markers, zidovudine (ZDV) use, hard drug use, and gestational age at delivery were not. When examined in a combined multivariate analysis of maternal characteristics, only vitamin A concentration independently predicted infant progression. Infant characteristics during the first 6 months of life that, by univariate analysis, were associated with disease progression included elevated mean viral load at 1 to 6 months of age, depressed CD4⁺%, CDC Clinical Disease 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 characteristics 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 maternal and infant characteristics in a multivariate analysis. It showed that factors independently predicting infant progression by 18 months of age were progression to CDC Category B by 6 months of age (OR, 5.80) and elevated 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 disease or death by 6 months of age were also examined. The only maternal characteristic associated with progression by 6 months in multivariate analysis was low maternal CD4⁺%. The infant characteristics associated with progression by 6 months of age in multivariate analysis were depressed mean CD4⁺% from birth through 2 months and the presence of lymphadenopathy, hepatomegaly, or splenomegaly by 3 months. Infant ZDV use was not assocciated with rapid progression.

Conclusion.  The strongest predictors of progression by 18 months are the presence of moderate clinical symptoms and elevated RNA copy number in the infants in the first 6 months of life. In contrast, progression by 6 months is associated with maternal and infant immune suppression, and the presence of infant clinical symptoms. The difference suggests that the key pathogenetic mechanisms responsible for progression may vary with age. These observations help provide direction for future pathogenesis research and assist in clinical care.  Key words:  human immunodeficiency virus type 1, infant, maternal, disease progression.

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