rHGH reduces central fat accumulation in adolescent lipodystrophy

Dr Alesandra Vigano was one of the first doctors to describe the incidence of lipodystrophy and reduced bone mineral density in her cohort of 100 children at University of Milan.

At this years Lipodystrophy meeting she reported results from a pilot study of growth hormone dosed at 0.028mg/Kg daily for 24 weeks in eight adolescents with visceral fat accumulation (defined as intra-abdominal tissue (IAT) content >41cm² by MRI scan at L4). This is less than the therapeutic rHGH dose for children with growth impairment. Abnormal glucose tolerance, diabetes or ongoing malignancies were exclusion criteria for the study.

Three boys and five girls with median age 15.7 years (range 13.7-18.5), with mean BMI 21 Kg/cm² with undetectable viral load on combination of 3TC/d4T+PI therapy for a median of almost seven years (range 64-83 months) received 24 weeks rGHG treatment and results were compared to 97 healthy HIV-negative children as a control group.

All children completed the course of treatment and experienced approximate mean reductions in trunk, leg, arm and total fat of -1.0, -0.1, -0.3 and -1.5 kg respectively, compared to increases of fat in each area seen in health controls.

Increases in mean lean mass of +1.5, +0.5, +1.6 and +3.1 kg in trunk, arms, legs and total lean mass were all significantly greater (approximately double) than lean mass increases in the control group.

IGF-1 levels (measured at week 4, 12 and 24) approximately doubled in all eight patients and although supraphisiological IGF-1 levels were detected in 5/8 (62%) of the patients and in 9/24 (37%) of measurements these levels were only 2-23% over upper limit normal. BMI, glucose and lipid profiles (fasting glucose, glucose and insulin AUC, HDL, LDL and total cholesterol, and triglyceride levels did not significantly change or worsen over the study period.

Side effects reported with adult use of rHGH (swollen joint and muscle ache or pain, carpal tunnel syndrome, nausea) were not reported. Notable bone mineral content also increased over 24 weeks (17.9 vs 19.5g, p=0.03).

4/8 patients achieved target of IAT <41cm² and rHGH was not continued as maintenance dose. The other 4 patients continued treatment with a higher dosage of rHGH.

The authors concluded that rGHG was safe and effective at the studies dose in decreasing IAT and trunk fat and increasing lean mass in HIV-positive adolescents with ARV-associated central fat accumulation.

Comment

It was not clear in the study whether limb fat loss was caused by rHGH treatment or because HAART regimens continued to include d4T, 3TC and a PI.

Adult management of lipoatrophy has particularly shifted from continued use of d4T, and more recently also from AZT, in any patient with symptomatic lipoatrophy, and the use of other nucleosides would seem equally appropriate in children and adolescents, particularly strengthened by related studies at this Workshop.

Although switching therapies is likely to be an easy approach for lipoatrophy, there is not such a clear option for fat accumulation, and rHGH may therefore be an important option. The safety data from this study was reassuring.

Durability of response will be important, as fat accumulation has returned in around 50% adults patients using rHGH,. Ongoing studies are looking at whether the response can be extended by lower dose maintenance regimens in these individuals.

A Viganò A et al. Effects of recombinant growth hormone on visceral fat accumulation: pilot study in HIV-infected adolescents. Abstract 01. Antiviral Therapy 2004; 9(6):L3.
http://www.aegis.org/DisaplayConf/?Abstract=87285