ECE2006 Poster Presentations Cytokines and growth factors (33 abstracts)
1Dept. of Infectious Diseases, Hvidovre University Hospital, Hvidovre, Copenhagen, Denmark; 2Clinical Research Unit, Hvidovre University Hospital, Hvidovre, Copenhagen, Denmark; 3Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus, Denmark; 4Dept. of Endocrinology and Internal Medicine, Hvidovre, Copenhagen, Denmark.
Objective: High dose growth hormone (rhGH) regimens (2 to 4 mg/day) have been shown to increase circulating insulin-like growth factor (IGF)-I to supra-physiological levels in human immunodeficiency virus (HIV)-infected patients on combined antiretroviral therapy (CART). This setting may improve immunologic output. However, a high plasma IGF-I concentration has detrimental effects on glucose metabolism, which hampers the use of high dose rhGH regimens.
Methods: We have reported previously on a group of 6 HIV-infected patients on stable CART (>28 months), in whom 16 weeks on rhGH 0.7 mg/day increased total (+117%, P<0.01) and free (+155%, P<0.01) IGF-I to high in physiological range. This study was extended to examine whether continued use of low-dose rhGH (0.7 mg/day until week 60; 0.4 mg/day from week 60 to week 140) would keep IGF-I expediently high in the normal range and improve CD4 T-cell response.
Results: Total and free IGF-I remained expediently increased at week 36 (+97%, P<0.01 and +125%, P<0.01) and week 60 (+77%, P=0.01 and +125%, P<0.01) compared to baseline (161±15 μg/l and 0.75±0.11 μg/l). CD4 T-cell count, which was unchanged after 16 weeks (P>0.7), was increased at week 36 (+15%, P<0.05) and week 60 (+31%, P=0.01), compared to baseline (CD4 456±55 cells/μl). After rhGH dose-reduction, total IGF-I remained increased at week 88 (+44%, P=0.01) and week 140 (+46%, P=0.07) compared to baseline, whereas free IGF-I returned to baseline (P>0.3). CD4 cell count remained increased at week 88 (+33%, P<0.01) and week 140 (+36%, P=0.02) compared to baseline.
Conclusions: These data suggest that a low-dose rhGH regimen through a substantial increment in circulating IGF-I may improve immunologic response in terms of increased CD4 T-cell output in HIV-infected patients on stable CART. A well-powered, randomized, double-blind, placebo-controlled clinical trial is ongoing aiming to validate these preliminary data.