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Abstract
Recombinant human growth hormone (r-hGH) to treat HIV-associated Adipose Redistribution Syndrome (HARS): 12-week (Wk) induction and 24-wk maintenance therapy (Tx)
Grunfeld C.1, Thompson M.2, Brown S.J.3, Richmond G.4, Lee D.A.5, Muurahainen N.6, Kotler D.P.7, and the Study 24380 Investigators Group
1UCSF-VA Med. Center, Div. of Endocrinology, San Francisco, United States, 2AIDS Research Consortium, Atlanta, Georgia, United States, 3AIDS Research Alliance, W. Hollywood, United States, 4Richmond Clinic, Fort Lauderdale, United States, 5UCSD, Antiviral Research Center, San Diego, United States, 6Serono, Inc., Clinical Development, Rockland, United States, 7Columbia/St Lukes-Roosevelt, GI Immunology, New York, United States
Background: Excess accumulation of truncal fat, including visceral adipose tissue (VAT), in HIV-infected persons (HARS) is associated with risks to health and psychosocial well-being. No therapies are currently approved to treat HARS.
Methods: Randomized, double-blind, placebo-controlled, multi-center trial, comparing effects of r hGH (Serostim®) to placebo (PL) in reducing VAT in HARS. Induction Therapy (Tx) was r hGH 4mg daily vs. PL from baseline to Wk 12. From Wks 12 to 36, pts who initially had r-hGH Induction Tx were randomized to r-hGH 2mg on alternate-days (Maintenance Tx) or PL. Patients who initially had PL (BL to Wk 24) later received r-hGH 4mg daily (Wks 24-36). Primary endpoint was change in cross-sectional VAT area on CT scan at L4-L5. Key secondary endpoints included change in non-HDL cholesterol (C) and limb fat (LF) by DXA.
Results: 325 pts received at least 1 dose of study drug. BL: age 44.8±7.1 years, 74.8% white; 85.4% male, HIV-1 RNA 400 copies/mL 81.7%, CD4+ count 499±282 cells/mm3. On Induction Tx, change in VAT area at 12 wks was -32.6±37.9cm2 on r-hGH and +0.5±34.5cm2 on PL (p<0.001). Compared to PL, pts on GH Induction Tx had decreased LF, and non-HDL-C (p<=0.023). During the Induction-Maintenance (BL to Wk 36), pts on r-hGH Maintenance Tx sustained reductions in VAT (-26.6±43.9cm2) from BL. Pts on PL maintenance sustained a small reduction in VAT (-10.0±39cm2). By 36 wks there were no changes in limb fat from BL in either group. At 36 wks, non-HDL-C remained decreased on r-hGH Maintenance Tx, but not on placebo. There were no unexpected AEs, no episodes of hyperglycemia or diabetes requiring therapeutic intervention.
Conclusions: In HARS pts, r-hGH 4mg daily Induction Tx for 12 weeks significantly reduced VAT, trunk fat, and non-HDL-C, and rhGH Maintenance Tx for 24 wks helped to sustain the clinical benefits.
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