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

TY - JOUR

T1 - Low-dose growth hormone therapy reduces inflammation in HIV-infected patients

T2 - a randomized placebo-controlled study

AU - Lindboe, Johanne Bjerre

AU - Langkilde, Anne

AU - Eugen-Olsen, Jesper

AU - Hansen, Birgitte R.

AU - Haupt, Thomas H.

AU - Petersen, Janne

AU - Andersen, Ove

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

KW - Adult

KW - Anti-Retroviral Agents

KW - C-Reactive Protein

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Growth Hormone

KW - HIV Infections

KW - Humans

KW - Inflammation

KW - Male

KW - Middle Aged

KW - Placebos

KW - Receptors, Urokinase Plasminogen Activator

KW - Treatment Outcome

KW - Young Adult

KW - Journal Article

KW - Randomized Controlled Trial

U2 - 10.1080/23744235.2016.1201722

DO - 10.1080/23744235.2016.1201722

M3 - Journal article

C2 - 27417288

SN - 2374-4235

VL - 48

SP - 829

EP - 837

JO - Infectious Diseases

JF - Infectious Diseases

IS - 11-12

ER -