A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF COMBINED INSULIN-LIKE GROWTH-FACTOR-I AND LOW-DOSE GROWTH-HORMONE THERAPY FOR WASTING ASSOCIATED WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Loss of body mass, or wasting, is a major cause of morbidity and a con tributor to mortality in human immunodeficiency virus-1 (HIV-1) infect ion. Dietary supplements and appetite adjuvants have had limited effec tiveness in treating this condition. GH and insulin-like growth factor I (IGF-I) have been shown to be anabolic in many catabolic conditions , and limited data suggest similar efficacy in HIV wasting. In additio n, it appears that GH and IGF-I may have complementary anabolic effect s with opposing glucoregulatory effects. We report results from a 12-w eek randomized, placebo-controlled trial of combination recombinant hu man GH (rhGH; Nutropin; 0.34 mg, sc, twice daily) and rhIGF-I (5.0 mg, sc, twice daily) in individuals with HIV wasting and without-active o pportunistic infection, cancer, or gastrointestinal disease. A total o f 142 subjects (140 males and 2 females) were randomized using a 2:1, double blind treatment scheme and assigned to receive either active tr eatment or placebo injections. Eighty subjects completed the 12-week p rotocol. Nutritional intake and demographic and clinical characteristi cs did not differ between the groups at any study time point. At 3 wee ks, the treatment group had a significantly larger weight increase (P = 0.0003), but this difference was not observed at any later time poin t. Similarly, fat-free mass, calculated from skinfold measurements, in creased transiently in the treatment group at 6 weeks (P = 0.002). No significant differences in isokinetic muscle strength or endurance tes ting or in quality of life were observed between the groups. Resting h eart rate was significantly higher in the treatment group at each time point post-baseline. GH and IGF-binding protein-3 levels did not chan ge; however, IGF-I levels were higher in the treatment group at 6 and 12 weeks. There were no significant between-group differences in any o f the measured biochemical or immunological parameters. rhGH plus rhIG F-I treatment was associated with an increased incidence of peripheral edema and other side-effects, possibly related to fluid retention. We conclude that the combination of rhIGF-I and low dose rhGH used in th is study had no significant anabolic effect in HIV wasting.