Growth Hormone Treatment of Children With HIV-Associated Growth Failure

Wasting, or loss of lean tissue, is a serious consequence of AIDS. Body composition findings in HIV-infected children are similar to those of HIV-uninfected children with classic growth hormone deficiency. Evidence suggests that therapeutic administration of growth hormone (GH) can induce anabolic effects, reverse pathologic catabolism, and perhaps even improve immune function. As survival to adolescence and beyond improves with modern therapy in children with HIV infection, it will become increasingly important to address the problems of stunting and short stature in this population. \[AS PER AMENDMENT 09/04/01: Recent evidence suggests that needle-free delivery is preferred by young children below the age of ten years. Given the advantages of a needle-free delivery system for the administration of growth hormone, most significantly the reduction of risk for HIV contaminated needle-stick injuries to care providers and other household members, it has been decided to use this method of study drug delivery for all study participants.\] Children are assigned randomly to 1 of the following treatment groups: Group 1: Children receive a single dose of r-hGH once a day. Group 2: Children receive half the dose of r-hGH that Group 1 receives, once a day. Group 3a: Children receive no r-hGH for the first 24 weeks \[AS PER AMENDMENT 01/03/01: 48 weeks\] of the study. After Week 24 \[AS PER AMENDMENT 01/03/01: Week 48\], they receive the same dose as that of Group 1. Group 3b: Children receive no r-hGH for the first 24 weeks \[AS PER AMENDMENT 01/03/01: 48 weeks\] of the study. After Week 24 \[AS PER AMENDMENT 01/03/01: Week 48\], they receive the same dose as that of Group 2. Subcutaneous injections are administered \[AS PER AMENDMENT 09/04/01: using a needle-free device\], daily for 96 weeks in Groups 1 and 2; after 24 weeks \[AS PER AMENDMENT 01/03/01: 48 weeks\] on study, the treatment-delayed control group (Group 3) receives injections for 72 weeks \[AS PER AMENDMENT 01/03/01: 48 weeks\]. The first injection is at the clinic and parents/guardians are trained how to prepare and administer the injections. Children are closely monitored for toxicity, with dosing adjustments if needed. Evaluations and laboratory tests are done at clinic visits every 4 weeks to determine growth indicators, body chemistries, CD4 cell counts, HIV-1 RNA PCR, and anti-hGH antibodies and for routine hematology testing, dietary intake assessment, and MRI scans. \[AS PER AMENDMENT 01/03/01: MRI scans are no longer performed.\]