Abstract 857 Poster Session I, Saturday, 5/1 (poster 287)

The Hemophilia Growth and Development Study (HGDS) followed 333 hemophilic boys and adolescents, approximately 62% of whom were infected with human immunodeficiency virus (HIV). Prior reports from the HGDS have documented delays in statural growth, skeletal (bone age) and sexual maturation in HIV + compared to HIV- study participants. The delays in maturation strongly suggest that part of the growth failure seen in HIV-infected children can be attributed to pubertal delay. Monitoring pubertal delay is important since delay in maturation may be an indicator of subsequent HIV-related symptom development. The purpose of the current investigation was to examine the effect of HIV RNA (viral load) and CD4 lymphocytes on height, bone age, and testosterone levels for 205 HIV + hemophiliacs followed over seven years. These HIV + participants were 13.1±3.1 years at entry with an estimated infection period of 6.7±0.9 years.

Height and bone age were measured repeatedly, testosterone levels were measured once. Viral load and CD4 were measured at baseline and annually throughout follow-up. The analyses examined the effect of viral load and also its effect in addition to CD4, after adjusting for age and ethinicity. Baseline viral load was a significant predictor for all three outcomes: 3-fold increases in baseline HIV RNA were associated with 1.62 cm decreases in height (p<0.001), 0.21 year decreases in bone age (p=0.005), and 1.29 ng/dl decreases in testosterone levels (p=0.002). However, HIV RNA changes over time (mean change = +1500 copies/ml/yr) failed to predict height (p=0.16) or bone age (p=0.30). Including CD4 with HIV RNA improved the prediction of height: 100-cell decreases in CD4 were associated with 2.51 cm decreases in height (p<0.001), while 3-fold increases in HIV RNA were associated with 0.95 cm decreases in height (p=0.039). Longitudinal changes in CD4 and viral load were, however, not significant. For bone age prediction, CD4 remained significant but HIV RNA did not. Both cross-sectional and longitudinal CD4 components were significant: 100-cell decreases in baseline CD4 and CD4 changes from baseline were associated with bone age decreases of 0.39 (p=0.002) and 0.21 (p=0.018) year respectively. Similarly, CD4 had a significant effect (p=0.008) predicting testosterone levels but HIV RNA did not. Antiretroviral treatment was not a significant predictor of any of three outcomes. Although 86% of study participants received antiretroviral therapy at some time during follow-up, there was minimal use of highly active antiretroviral therapy (HAART). In conclusion, HIV RNA was a significant predictor of delayed/decreased height, bone age, and testosterone levels but, after accounting for CD4, was only predictive of shorter stature.