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 a s somatropin) is human growth hormone produced by recombinant DNA tech nology. Somatropin, an established treatment for growth hormone-defici ent children of short stature, has recently been shown to have benefic ial effects in adult patients with HIV-associated wasting. This condit ion is characterized by the preferential loss of lean body mass (LBM) with relative conservation of body fat. Somatropin produces protein an abolic and anticatabolic effects in patients with HIV-associated wasti ng. In HIV-infected male patients with this condition, increased nitro gen retention, decreased protein oxidation, increased lipid oxidation, increased bodyweight and increased resting energy expenditure were ev ident after treatment with subcutaneous somatropin 0.1 mg/kg/day for 7 days. Statistically significant increases in LBM, bodyweight (vs base line and placebo) and work output (vs placebo) during treadmill exerci se (a measure of physical function), and a significant decrease in bod y fat (vs baseline and placebo) occurred in similar patients who recei ved somatropin for 12 weeks in a large double-blind randomised trial. These patients received concomitant antiretroviral therapy for the dur ation of the trial. Available data indicate that somatropin does not i ncrease HIV replication in patients with HIV disease who are receiving concomitant antiretroviral medication. The inconclusive results of qu ality-of-life assessments in patients with HIV-associated wasting rece iving treatment with somatropin may have been related to the lack of a suitable instrument for measuring quality of life in this patient pop ulation. Further investigation is required to definitively establish t he effects of the drug on this outcome measure. Adverse events commonl y observed with somatropin administered over less than or equal to 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 eltents ass ociated with somatropin are generally mild to moderate in severity and resolve after dosage reduction or discontinuation of somatropin treat ment. The longer term tolerability profile of the agent in patients wi th HIV-associated wasting requires further clarification, however; unp ublished data indicate that incidences of somatropin-related adverse e vents diminish over time. In conclusion, somatropin appears to be a us eful short term treatment for adult patients with HIV-associated wasti ng who continue to receive treatment with at least 2 antiretroviral dr ugs. Somatropin increases lean tissue, decreases body fat and improves physical function. Future pharmacoeconomic analyses may show that som atropin therapy has the potential to reduce direct healthcare costs, a s a result of reduced time spent in hospital and less dependence on ho mecare support because of improved physical function. Although the ult imate positioning of somatropin has yet to be defined, recent data sug gest that its role in the treatment of patients with HIV-associated wa sting may be that of a short term intervention therapy, rather than a continuous treatment.