T Sivakumar1, Oj Mechanic, D A Fehmie, Bt Paul. 1. Endocrinology Department, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. doctor_sivakumar@hotmail.com
Abstract
BACKGROUND: HIV-associated lipodystrophy is a disorder of fat metabolism that occurs in patients with HIV infection. It can cause metabolic derangements and negative self-perceptions of body image, and result in noncompliance with highly active antiretroviral therapy (HAART). Growth hormone (GH) axis drugs have been evaluated for treatment of this disorder, but no systematic review has been conducted previously. OBJECTIVES: The aim of the review was to compare the effects of GH axis drugs vs. placebo in changing visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and lean body mass (LBM) in patients with HIV-associated lipodystrophy. SEARCH METHODS: We searched MEDLINE (1996-2009), CENTRAL (Issue 4, 2009), Web of Science, Summons, Google Scholar, the Food and Drug Administration (FDA) website, and Clinicaltrials.gov from 13 October 2009 to 7 June 2010. We excluded newspaper articles and book reviews from the Summons search; this was the only search limitation applied. We also manually reviewed references of included articles. SELECTION CRITERIA: Inclusion criteria were as follows: randomized placebo-controlled trial (RCT); study participants with HIV-associated lipodystrophy; intervention consisting of GH, growth hormone releasing hormone (GHRH), tesamorelin or insulin-like growth factor-1 (IGF-1); study including at least one primary outcome of interest: change in VAT, SAT or LBM. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and assessed study quality using a standardized form. The authors of one study were contacted for missing information. The main effect was calculated as a summary of the mean differences in VAT, SAT and LBM between the intervention and placebo groups in the included studies. Subgroup analyses were performed to assess different GH axis drug classes. RESULTS: Ten RCTs including 1511 patients were included in the review. All had a low risk of bias and passed the test of heterogeneity for each primary outcome. Compared with placebo, GH axis treatments decreased VAT [weighted mean difference (WMD) -25.20 cm(2) ; 95% confidence interval (CI) -32.18 to -18.22 cm(2) ; P<0.001] and increased LBM (WMD 1.31 kg; 95% CI 1.00 to 1.61 kg; P<0.001], but had no significant effect on SAT mass (WMD -3.94 cm(2) ; 95% CI -10.88 to 3.00 cm(2) ; P=0.27]. Subgroup analyses showed that GH had the most significant effects on VAT and SAT, but none on LBM. The drugs were well tolerated but statistically significant side effects included arthralgias and oedema. CONCLUSIONS: Our review indicates that, based on the findings of the 10 included studies, GH axis treatments are effective in reducing VAT and increasing LBM in patients with HIV-associated lipodystrophy. However, clinicians must decide whether the attributed benefits are clinically significant, considering the costs and potential risks of GH axis treatments. A limitation of this study is the small number of studies available of each GH axis drug class.
BACKGROUND: HIV-associated lipodystrophy is a disorder of fat metabolism that occurs in patients with HIV infection. It can cause metabolic derangements and negative self-perceptions of body image, and result in noncompliance with highly active antiretroviral therapy (HAART). Growth hormone (GH) axis drugs have been evaluated for treatment of this disorder, but no systematic review has been conducted previously. OBJECTIVES: The aim of the review was to compare the effects of GH axis drugs vs. placebo in changing visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and lean body mass (LBM) in patients with HIV-associated lipodystrophy. SEARCH METHODS: We searched MEDLINE (1996-2009), CENTRAL (Issue 4, 2009), Web of Science, Summons, Google Scholar, the Food and Drug Administration (FDA) website, and Clinicaltrials.gov from 13 October 2009 to 7 June 2010. We excluded newspaper articles and book reviews from the Summons search; this was the only search limitation applied. We also manually reviewed references of included articles. SELECTION CRITERIA: Inclusion criteria were as follows: randomized placebo-controlled trial (RCT); study participants with HIV-associated lipodystrophy; intervention consisting of GH, growth hormone releasing hormone (GHRH), tesamorelin or insulin-like growth factor-1 (IGF-1); study including at least one primary outcome of interest: change in VAT, SAT or LBM. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and assessed study quality using a standardized form. The authors of one study were contacted for missing information. The main effect was calculated as a summary of the mean differences in VAT, SAT and LBM between the intervention and placebo groups in the included studies. Subgroup analyses were performed to assess different GH axis drug classes. RESULTS: Ten RCTs including 1511 patients were included in the review. All had a low risk of bias and passed the test of heterogeneity for each primary outcome. Compared with placebo, GH axis treatments decreased VAT [weighted mean difference (WMD) -25.20 cm(2) ; 95% confidence interval (CI) -32.18 to -18.22 cm(2) ; P<0.001] and increased LBM (WMD 1.31 kg; 95% CI 1.00 to 1.61 kg; P<0.001], but had no significant effect on SAT mass (WMD -3.94 cm(2) ; 95% CI -10.88 to 3.00 cm(2) ; P=0.27]. Subgroup analyses showed that GH had the most significant effects on VAT and SAT, but none on LBM. The drugs were well tolerated but statistically significant side effects included arthralgias and oedema. CONCLUSIONS: Our review indicates that, based on the findings of the 10 included studies, GH axis treatments are effective in reducing VAT and increasing LBM in patients with HIV-associated lipodystrophy. However, clinicians must decide whether the attributed benefits are clinically significant, considering the costs and potential risks of GH axis treatments. A limitation of this study is the small number of studies available of each GH axis drug class.
Authors: Andrea Bortolato; Andrew S Doré; Kaspar Hollenstein; Benjamin G Tehan; Jonathan S Mason; Fiona H Marshall Journal: Br J Pharmacol Date: 2014-07 Impact factor: 8.739