10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 6-8 November 2008, London, UK

THE IMPACT OF SWITCHING DOUBLE-BOOSTED PROTEASE INHIBITORS TO DARUNAVIR/RITONAVIR ON INSULIN SENSITIVITY

Antiviral Therapy 2008; 13(Suppl. 4):A30 (abstract no. P-11)

P Randell, A Jackson, M Nelson and G Moyle
Chelsea & Westminster Hospital, London, UK

BACKGROUND: Double-boosted protease inhibitors (DBPIs) are used in the treatment of experienced patients who have resistance to or intolerance of drugs from other available classes. There is insufficient data available to support this approach and there is concern that long-term side effects of PIs may be potentiated. The advent of newer drugs has opened the possibility of rationalizing the treatment of these patients, potentially reducing toxicity.

METHODS: This open-label, prospective, cohort study investigated the effect of substituting ritonavir-boosted darunavir (DRV/r) for DBPIs on insulin sensitivity. Ten HIV-positive male patients were enrolled. They were stable on a DBPI regimen with no prior evidence of DRV resistance-associated mutations. A hyperinsulinaemic euglycaemic clamp was performed at baseline and repeated after 4 weeks of twice daily DRV 600 mg and ritonavir 100 mg. All other drugs in the initial regimen were continued.

RESULTS: Five patients were switched to DRV/r monotherapy and five received DRV/r in addition to their nucleoside reverse transcriptase inhibitors. All patients maintained an undetectable viral load after 4 weeks of treatment. There was a mean (±sem) percentage increase of 16.2% (±9.1) from baseline for the peripheral glucose disposal rate (GDR; P=0.160). Subjects were divided according to their baseline GDR; the five patients with a GDR less than the median (5.05 mg/kg/min) had a mean (±sem) increase of 31.3% (±14.5). In contrast, the five patients whose GDR was above the median only demonstrated an increase of 1.1% (±6.85). There was no significant change in CD4+ T-cell counts and lipid parameters after 4 weeks of switching treatment.

CONCLUSIONS: In patients switching from a DBPI regimen to DRV/r, virological control was maintained after 4 weeks. Overall, there was no deleterious impact on insulin sensitivity with the switch and in patients with lower insulin sensitivity at baseline there was evidence of an improvement. There was no short-term effect on lipid homeostasis.

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2008-11-06
P-11

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