Low-dose growth hormone therapy reduces inflammation in HIV-infected patients: a randomized placebo-controlled study

Abstract

Background: Combination antiretroviral therapy (cART) has drastically increased the life expectancy of HIV-infected patients. However, HIV-infected patients exhibit increased inflammation and 33–58% exhibit a characteristic fat re-distribution termed HIV-associated lipodystrophy syndrome (HALS). Recombinant human growth hormone (rhGH) has been tested as treatment of HALS. Low-dose rhGH therapy improves thymopoiesis and fat distribution in HIV-infected patients and appears to be well tolerated. However, since high-dose rhGH is associated with adverse events related to inflammation, we wanted to investigate the impact of low-dose rhGH therapy on inflammation in HIV-infected patients.

Methods: Forty-six cART-treated HIV-infected men were included in the HIV-GH low-dose (HIGH/Low) study: a randomized, placebo-controlled, double-blinded trial. Subjects were randomized 3:2 to 0.7 mg/day rhGH, or placebo for 40 weeks. rhGH was self-administered between 1 pm and 3 pm. The primary outcome of this substudy was changes in inflammation measured by plasma C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR).

Results: Both CRP (−66%, p = 0.002) and suPAR (−9.7%, p = 0.06) decreased in the rhGH group compared to placebo; however, only CRP decreased significantly. The effect of rhGH on inflammation was not mediated through rhGH-induced changes in insulin-like growth factor 1, body composition, or immune parameters.

Conclusion: Daily 0.7 mg rhGH treatment for 40 weeks, administered at nadir endogenous GH secretion, significantly reduced CRP. The effect does not appear to be mediated by other factors. Our findings suggest that low-dose rhGH treatment may minimize long-term risks associated with high-dose rhGH therapy.

Keywords:

• CRP
• IGF-1
• lipodystrophy
• suPAR

Acknowledgements

We are grateful to the individuals of this study for their participation, patience, and cooperation. The authors wish to thank Arild Ejsing and Jette Nymann for assistance with laboratory analysis, together with Line Jee Hartmann Rasmussen, Ane-Katrine Skielboe, and Juliette Tavenier for fruitful discussions. Moreover, we are very grateful for the financial support from Agnethe Løvgreens scholarship and Hvidovre Hospitals Forskningsfond.

Disclosure statement

Jesper Eugen-Olsen and Ove Andersen are inventors of a patent on suPAR and disease risk, which is owned by Hvidovre Hospital and licensed to ViroGates A/S. Jesper Eugen-Olsen is the CSO, founder, and a shareholder in ViroGates A/S. Johanne B. Lindboe, Anne Langkilde, Thomas H. Haupt, Birgitte R. Hansen, and Janne Petersen declare no conflicts of interest. Agnethe Løvgreens scholarship and Hvidovre Hospitals Forskningsfond provided funding. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.