INVITRO INSULIN-LIKE GROWTH FACTOR-I, GROWTH-HORMONE, AND INSULIN-RESISTANCE OCCURS IN SYMPTOMATIC HUMAN IMMUNODEFICIENCY VIRUS-1-INFECTED CHILDREN

Poor growth is a common feature of symptomatic children (Centers for D isease Control stage P2) infected with human immunodeficiency virus-1 (HIV-1). However, several previous studies have failed to show any rel ationship between serum hormone levels and poor growth. To assess the roles of hormone deficiency and hormone resistance in the development of poor growth in HIV-1-infected children, we studied six asymptomatic Centers for Disease Control stage P1 height SD score = 0.01 +/- 1.0 (mean +/- SD)!, 10 P2 (height SD score = -2.0 +/- 1.0), and six short, normal children (height SD score = 2.4 +/- 1.2). Mean weight:height S D scores were similar in all three groups, suggesting that gross nutri tional status did not differ between groups. There were no significant differences between groups with respect to mean plasma levels of IGF- I, thyroid hormones, TSH, and cortisol. As an index of hormone sensiti vity, we quantified in vitro colony formation of erythroid progenitor cells, isolated from peripheral blood of study subjects, in response t o IGF-I, growth hormone (GH), and insulin. P2 subjects had a quantitat ive mean reduction in erythroid progenitor cells colony formation in r esponse to IGF-I of 32% compared with P1 subjects (p = 0.001 by analys is of variance) and 21% compared with controls (p = 0.006); in respons e to GH of 21% compared with controls (p = 0.015); and in response to insulin of 35% compared with P1 subjects (p = 0.038) and 34% compared with controls (p = 0.004). Similar qualitative differences (changes in shape) of the three hormone response curves between P2 and P1 and P2 and control subjects were observed. No differences in either quantitat ive or qualitative erythroid progenitor cells responses to IGF-I, GH, or insulin between P1 and control subjects were observed. We conclude that more severe HIV-1 infection in children is associated with in vit ro resistance to the growth-promoting actions of IGF-I, GH, and insuli n that is unrelated to the presence of gross malnutrition, differences in hematologic status, or overwhelming illness. This resistance to IG F-I could contribute to the poor in vivo growth seen in symptomatic HI V-1-infected children.