333    

Background:  HIV-related wasting is a common complication of HIV infection that is often undiagnosed and untreated. Loss of lean body mass (LBM) strongly predicts progression to AIDS or death, independent of CD4⁺ cell count. Among the myriad of factors contributing to wasting, growth hormone deficiency is a frequently observed endocrine manifestation. Recombinant human growth hormone (r-hGH) is indicated for treatment of wasting and may also have immunostimulant activity. Ghrelin, a recently discovered peptide hormone regulating nutrient in-take and metabolism, is the first endogenous growth hormone secretagogue to be identified. The interplay between ghrelin and r-hGH has never been studied in HIV-related wasting. We hypothesize that differences in ghrelin levels between AIDS patients and normal controls may mediate differences in r-hGH levels in the pathogenesis of HIV-related wasting.

Methods:  All subjects were African American. To capture circadian variation in hormone levels, 8 plasma samples were collected over a 14-hour period from seronegative controls (n = 6) and patients with AIDS and wasting (n = 3). Samples were assayed for active ghrelin by radioimmunoassay. Assays for r-hGH were ongoing. Body mass index (BMI), LBM, and basal metabolic rate (BMR) were measured using a Tanita Body Composition Analyzer (model TBF-215).

Results:  Differences between controls and AIDS patients were observed in mean ghrelin levels (663.7 + 55.27 pg/mL vs 398.8 + 66.6), peak ghrelin levels (1248.8 + 71.1 vs 988.6 + 39.7), trough ghrelin levels (149.8 + 62.3 vs 26 + 4.2), somatomedin C/IGF-1 (140 + 19.5 vs 254 + 2.54) and area-under-curve (AUC) for ghrelin (9572.5 + 962 vs 5964.2 +  696), respectively. Analyses of all subjects showed a positive correlation between somatomedin C and BMR (r = 0.86, p = 0.01), and inverse correlations between peak ghrelin and somatomedin C (r = -0.91, p = 0.004), mean ghrelin and somatomedin C (r=-0.73, p = 0.059), peak ghrelin and BMR ( = -0.69, p = 0.057), and somatomedin C and ghrelin AUC (r= -0.69, p = 0.08).

Conclusions:  Our observations, while preliminary, provide the first evidence for an association between ghrelin levels and HIV-related wasting. Because of the role of ghrelin in r-hGH secretion, deficiencies in ghrelin may underlie r-hGH deficiency in advanced HIV disease. Ghrelin may be a novel target for treatment of wasting and immune deficiency in HIV disease.

Keywords: HIV-related wasting; ghrelin; growth hormone