1st International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 26–28 June 1999 - San Diego, CA, USA

AMPRENAVIR: A NEW PROTEASE INHIBITOR WITH A FAVOURABLE METABOLIC PROFILE

Antiviral Therapy 1999; 4(Suppl. 2):52(abstract no. 34)

L Pedneault¹, C Hanson¹, P Nacci², A Fetter², J Millard¹ and M Rogers^1
1Glaxo Wellcome HIV/OI Clinical Development, Research Triangle Park, North Carolina, USA; and ²Glaxo Wellcome HIV/OI Clinical Development, Greenford, UK

BACKGROUND: Metabolic complications such as abnormal fat redistribution (FR), diabetes mellitus (DM), hypertriglyceridaemia (TG), hypercholesterolaemia (CH), and hyperglycaemia (GL) have been reported in HIV-infected subjects receiving protease inhibitors (PIs). However, a causal relationship has not been established.

OBJECTIVES: To characterize the metabolic profile of amprenavir when compared to placebo and to indinavir in HIV-infected subjects.

DESIGN: Data related to potential metabolic complications (FR, DM, TG, CH, GL) were collected from four amprenavir clinical trials conducted in different patient populations with various treatment regimens. Potential cases of FR were reviewed. Blood samples were not collected in fasting conditions.

RESULTS: A total of 490 subjects received amprenavir as part of studies PROAB3001 (plus zidovudine/lamivudine, n=113; treatment-naïve), PROAB3006 (plus two NRTIs, n=245; NRTI-experienced), PROA2001 (plus zidovudine/lamivudine, n=9, plus another PI, n=24; PI-naïve), CNAA2007 (plus abacavir/efavirenz, n=99; NRTI, PI, ±NNRTI-experienced). The control groups consisted of subjects receiving placebo/zidovudine/lamivudine in study PROAB3001 (n=109) and subjects receiving indinavir and two NRTIs in study PROAB3006 (n=241). Over 48 weeks, symptoms of FR were reported infrequently among subjects receiving amprenavir. In PROAB3006, 11 cases were reported in indinavir-treated subjects versus four in amprenavir treated subjects. In PROAB3001, there was one case in the amprenavir group versus 0 on placebo. Six cases were reported in the heavily pretreated PI-experienced subjects in CNAA2007; no case was reported in subjects treated with two PIs in PROA2001. One subject with a family history of DM experienced DM while treated with amprenavir. Marked de novo elevations in TG, GL, and CH were infrequent: TG >750 mg/dl in 5%, 4%, 1%, and 29%, and GL >250 mg/dl in 1%, 3%, 1%, and 8% of subjects receiving amprenavir (n=455), indinavir (n=238), placebo (n=108) and dual PI (n=24), respectively; CH >320 mg/dl in <1% in all groups. Median values of TG, GL and CH remained within normal ranges in all treatment groups of PROAB3001 and PROAB3006, although slight increases in median CH levels were observed. However, in PROA2001, elevations in median TG and CH were slightly more pronounced with dual PI regimens than with amprenavir/zidovudine/lamivudine. In CNAA 2007, median baseline values of TG and CH were marginally elevated and remained unchanged.

CONCLUSIONS: Amprenavir is a new PI with a favourable metabolic profile. Marked elevations in TG, GL and CH levels were infrequent. However, slight elevations in TG levels were observed more frequently with dual PI regimens. Our data suggest that previous treatment history might be predictive of FR.

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