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Micronutrient and Cytokine Interaction in Congenital Pediatric HIV Infection^1,2,

Susanna Cunningham-Rundles^*,,3, Sang Hyun Kim^*,,, Ann Dnistrian, Lenora Noroski^*,,, Celia Menendez-Botet, Claudia B. Grassey^**,,, Gilberto Hinds^**,, and Joseph S. Cervia^**,,

^* The Immunology Research Laboratory, Division of Pediatric Hematology Oncology Department of Clinical Chemistry, The Memorial Sloan Kettering Cancer Center, New York, New York, 10021 ^** Division of Infectious Disease Department of Pediatrics, The New York Hospital Cornell University Medical Center

Malnutrition is a frequent manifestation of HIV infection that has received comparatively little attention despite growing clinical importance with improved treatment and lengthened survival times. Fundamental relationships and mechanisms of HIV viral interaction in nutrient metabolism remain to be established. In an attempt to begin to fill the void of information relative to pediatric HIV infection, we have summarized the extant knowledge with regard to micronutrients and present some of the data from studies performed in our laboratory. Previous studies have shown both that vitamin A deficiency is associated with increased mortality in HIV + intravenous drug users and that maternal vitamin A deficiency is a risk factor for transmission in congenital exposure. Our most significant finding is that 70% of children congenitally exposed to HIV are vitamin A-deficient in the first months of life compared to age-matched controls whether they are HIV-infected or not. About 25% of our patient population was found to have growth or developmental delay, frequently without other signs of progression and in the presence of an intact T-cell compartment. In addition, we found evidence of cytokine imbalance, specifically elevated plasma levels of TNF which has been implicated in loss of lean body mass. Inflammatory reactions in the mucosa and increased TNF production in association with regional HIV infection may compromise gastrointestinal absorption. Based on the review of the literature and our research findings, it is clear that understanding the interaction between nutrients and both the regional and systemic immune system is vital for intervention and effective nutrient repletion in congenital HIV infection.

KEY WORDS: • HIV infection • malnutrition • micronutrients • growth • vitamins • minerals • metabolism • tumor necrosis factor (TNF)

¹ Presented at the workshop entitled "Nutrition in Pediatric HIV Infection: Setting the Research Agenda" held in Bethesda, MD on September 28–29, 1995. The workshop was sponsored by the Office of AIDS Research of the National Institutes of Health, the National Institute of Child Health and Human Development, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, Food and Drug Administration, Pediatric AIDS Foundation, National Dairy Council, Sandoz Nutrition Corporation, Bristol-Meyers Squibb Company, Clintec Nutrition Company, Ross Products Division-Abbott Laboratories, Serono Laboratories, Inc., and the American Institute of Nutrition. Workshop proceedings are published as a supplement to The Journal of Nutrition. Guest Editors for this supplement publication were Daniel J. Raiten and John M. Talbot, Life Sciences Research Office, Federation of American Societies for Experimental Biology, Bethesda, MD.

² The authors gratefully acknowledge the support of The Pediatric AIDS Foundation Grant: #500384-14-PG, NIH RO1 A135517, NIH-NCI 29529, The Children's Blood Foundation, The Helena Rubenstein Foundation, and The Aaron P. Diamond Foundation.

³ To whom correspondence should be addressed: Pediatric Hematology Oncology, Cornell University Medical College, 1300 York Avenue, New York, New York, 10021.