Sustained Low-Dose Growth Hormone Therapy Optimizes Bioactive Insulin-Like Growth Factor-I Level and May Enhance CD4 T-Cell Number in HIV Infection

High-dose recombinant human growth hormone (rhGH) (2-6 mg/day) regimes may facilitate T-cell restoration in patients infected with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART). However, high-dose rhGH regimens increase insulin-like growth factor-I (IGF-I) to supra-physiological levels associated with severe side effects. The present study investigated whether lower doses of rhGH may improve T-cell restoration in patients infected with HIV following an expedient response of total and bioactive (i.e., free) IGF-I. A previous 16-week pilot-study included six HIV-infected patients on stable HAART to receive rhGH 0.7mg/day, which increased total (+117%, P<0.01) and free (+155%, P<0.01) IGF-I levels. The study was extended to examine whether continuous use of low-dose rhGH (0.7 mg/day until week 60; 0.4 mg/day from week 60 to week 140) would maintain expedient IGF-I levels and improve CD4 T-cell response. Total and free IGF-I increased at week 36 (+97%, P<0.01 and +125%, P<0.01, respectively) and week 60 (+77%, P=0.01 and +125%, P<0.01) compared to baseline levels (161 +/- 15 and 0.75 +/- 0.11 mu g/L). CD4T-cell number increased at week 36 (+15%, P<0.05) and week 60 (+31%, P=0.01) compared to baseline levels (456 +/- 55cells/mu L). Following rhGH dose reduction, total IGF-I and CD4 T-cell number remained increased at week 88 (+44%, P=0.01 and +33%, P<0.01) and week 140 (+46%, P=0.07 and +36%, P=0.02) compared to baseline levels. These data support the notion that low-dose rhGH regimens may increase expediently total and bioactive IGF-I and improve T-cell restoration in patients infected with HIV on HAART. J. Med. Virol. 82:197-205, 2010. (C) 2009 Wiley-Liss, Inc.