791 Safety and Efficacy of Short-term Treatment with Growth Hormone and Thalidomide in HIV-infected Patients with a Secondary Infection: A Randomized, Double-blind, Placebo-controlled, Multi-center Trial M. Schambelan*1,2, K. Mulligan1,2, P. Bacchetti1, K. L. Johansen1,3, S. Bhasin4, C. Grunfeld1,3, D. P. Kotler5, S. Hulley1 1Univ of California at San Francisco; 2San Francisco Gen Hosp, CA; 3Veterans Admin Med Ctr, San Francisco, CA; 4Charles R Drew Univ, Los Angeles, CA; and 5St Luke's-Roosevelt Hosp Ctr, New York, NY
Background: Rapid weight loss often occurs during secondary infection (SI). This study was designed to determine whether short-term treatment with a protein anabolic agent (growth hormone [GH]) or a putative TNFalpha suppressor (thalidomide [TH]) could enhance weight and lean body mass (LBM) and provide a functional benefit and to investigate the safety and mechanisms of action of each agent in this setting.
Methods: We recruited 74 HIV+ patients (pts) with newly diagnosed SIs (primarily PCP and bacterial pneumonia) at 4 sites. Initially, they were randomized to receive GH (6 mg/d sc), TH (200 mg/d po), or placebo (PL) for 4 wks, in addition to standard SI treatment. In an interim review, the DSMB discontinued the TH arm for apparent lack of efficacy; thus, the final distribution was GH = 27, TH = 20, PL = 27. All but 3 pts were hospitalized at baseline. Weight, body composition (DEXA), resting energy metabolism (indirect calorimetry), viral load, CD4 count, and quality of life (QOL) were measured at baseline and 1, 2, 4, and 8 wks after randomization. Safety was assessed throughout.
Results: Eighty percent (80%) and 76% completed 4 and 8 wks of study, respectively. There were no clinically relevant differences among groups in changes in viral load, CD4 count, or serious adverse events (including deaths: 2 GH, 1 TH, 3 PL). Efficacy results are reported for GH and PL only. Median weight change after the 4-wk treatment period was +2.0 kg and +1.9 kg in GH and PL, respectively (p = 0.28 for GH vs PL). In the GH group, weight gain was exclusively LBM (+3.21 kg vs +0.65 kg; p = 0.009). Fat tended to decrease in GH and increase in PL (-0.49 kg and +0.56 kg, respectively; p = 0.043). Resting energy expenditure increased and respiratory quotient decreased (reflecting increased lipid oxidation) in GH but changed little in PL. At wk 8 (4 wks after discontinuation of study medication), the median change in LBM was +2.11 kg and +1.51 kg in GH and P, respectively (p = 0.20). Karnofsky score and self-reported physical functioning improved in both GH and PL, but there were no statistically significant differences between groups in these outcomes, nor in overall rating of QOL, at wk 8.
Conclusions: Administration of both GH and TH appears to be safe in the setting of SI. GH treatment resulted in an exclusive accrual of LBM, whereas weight gain with PL was evenly distributed between LBM and fat. By wk 8 the difference between GH and PL in LBM gain was minimal.
