Switching PI Therapy to Amprenavir & The Affect on Lipodystrophy & Lipids

Reduction in lipid abnormalities during treatment with amprenavir in subjects experiencing hyperlipidemia on a PI containing regimen
      L. Pedneault, C. Garris, S. Castillo, M. Rogers, N. Graham, L. Garrett, B. Akil, T. Scott, Glaxo Wellcome, and Beverly Hills, Calif.

Previous reports suggested in vitro and in vivo that amprenavir may have less adverse affect on metabolic changes (lipoatrophy and elevated lipids) than other protease inhibitors. This Glaxo Wellcome study aimed to assess the safety & tolerability of amprenavir on lipid metabolism in subjects experiencing hyperlipidemia with or without lipodystrophy. Patients were given open-label amprenavir with at least 2 other ART drugs. Concomitant use of other PI was not allowed. Subjects were required to have at least 4 weeks prior PI use. Subjects had to have grade 1-4 hyperlipidemia. Fasting blood samples, anthropometric measures & lipodystrophy signs & symptoms were collected at 12 week intervals.

Preliminary results:

• at week 12, the median change from baseline triglycerides, cholesterol & glucose was a decrease of 86 mg/dl (n=47), 6 mg/dl (n=47) and 3 mg/dl (n=48)
  
• Week 48: median change from baseline in triglycerides cholesterol & glucose was decrease of 364 mg/dl (n=13), decrease of 29 mg/dl (n=13), and increase of 7 mg/dl (n=12), respectively
  
• Body Composition measures did not change throughout the study: anthropometric measures, weight and signs & symptoms of lipodystrophy
  
• Median time on amprenavir was 272 days
  
• Amprenavir based adverse events reported >5% of subjects were nausea (12%), diarrhea (8%), oral/perioral parasthesia (7%), rash (7%), fatigue (6%). Authors characterized adverse events as mild to moderate
  
• Grade 3/4 adverse events were reported in 7% of subjects
  
• Authors reported that overall, viral load and CD4s were maintained

As you may know a new version of amprenavir is in phase 3 clinical study. The pill burden is greatly reduced. The antiviral efficacy and side effect profile results from this study will be important in assessing the usefulness of the new amprenavir.