Recombinant Mammalian Cell-Derived Somatropin: A Review of its Pharmacological Properties and Therapeutic Potential in the Management of Wasting Associated with HIV Infection.
Recombinant mammalian cell-derived somatropin (hereafter referred to as somatropin) is human growth hormone produced by recombinant DNA technology. Somatropin, an established treatment for growth hormone-deficient children of short stature, has recently been shown to have beneficial effects in adult patients with HIV-associated wasting. This condition is characterised by the preferential loss of lean body mass (LBM) with relative conservation of body fat. Somatropin produces protein anabolic and anticatabolic effects in patients with HIV-associated wasting. In HIV-infected male patients with this condition, increased nitrogen retention, decreased protein oxidation, increased lipid oxidation, increased bodyweight and increased resting energy expenditure were evident after treatment with subcutaneous somatropin 0.1 mg/kg/day for 7 days. Statistically significant increases in LBM, bodyweight (vs baseline and placebo) and work output (vs placebo) during treadmill exercise (a measure of physical function), and a significant decrease in body fat (vs baseline and placebo) occurred in similar patients who received somatropin for 12 weeks in a large double-blind randomised trial. These patients received concomitant antiretroviral therapy for the duration of the trial. Available data indicate that somatropin does not increase HIV replication in patients with HIV disease who are receiving concomitant antiretroviral medication. The inconclusive results of quality-of-life assessments in patients with HIV-associated wasting receiving treatment with somatropin may have been related to the lack of a suitable instrument for measuring quality of life in this patient population. Further investigation is required to definitively establish the effects of the drug on this outcome measure. Adverse events commonly observed with somatropin administered over </=12 weeks include tissue swelling or puffiness, arthralgia or myalgia and diarrhoea. These events occurred in significantly more somatropin than placebo recipients in a large double-blind trial. Adverse events associated with somatropin are generally mild to moderate in severity and resolve after dosage reduction or discontinuation of somatropin treatment. The longer term tolerability profile of the agent in patients with HIV-associated wasting requires further clarification; however, unpublished data indicate that incidences of somatropin-related adverse events diminish over time. In conclusion, somatropin appears to be a useful short term treatment for adult patients with HIV-associated wasting who continue to receive treatment with at least 2 antiretroviral drugs. Somatropin increases lean tissue, decreases body fat and improves physical function. Future pharmacoeconomic analyses may show that somatropin therapy has the potential to reduce direct healthcare costs, as a result of reduced time spent in hospital and less dependence on homecare support because of improved physical function. Although the ultimate positioning of somatropin has yet to be defined, recent data suggest that its role in the treatment of patients with HIV-associated wasting may be that of a short term intervention therapy, rather than a continuous treatment.
Perry
C M
CM
Adis International Limited, Auckland, New Zealand.
Wagstaff
A J
AJ