Conference Reports for NATAP

7th International Congress on Drug Therapy in HIV Infection November, 14-18, 2004 Glasgow, UK Back

NRTI-Sparing Fuzeon Study & Lipoatrophy       "An open label study to determine the efficacy and safety of enfuvirtide in patients changing therapy to an NRTI sparing regimen"   Reported By Jules Levin   Authors-David Cooper1, Dominic Dwyer 2 , Cassy Workman 3 , Janaki Amin 1 , John Miller 4 , Gillian Hales 1 , Sean Emery 1. 1University of New South Wales, Sydney, Australia; 2Westmead Hospital, Sydney, Australia; 3AIDS Research Initiative, Sydney, Australia; 4Roche Pharmaceuticals, Sydney, Australia   Note from Jules Levin: There is increasing interest in NRTI-sparing regimens due to the association between nukes & lipoatrophy. Although, tenofovir & abacavir do not appear to be associated with lipoatrophy. In particular, the development of entry inhibitors (fusion, CCR5 & attachment) provide opportunities to explore this. GSK's development program for their CCR5 inhibitor '140' will examine nuke sparing regimens.   The Alliance Study examined the use of enfuvirtide and NRTI-sparing regimens in heavily pre-treated patients.   57 HIV-1 positive, triple class experienced patients with current or prior NRTI treatment intolerance were enrolled in an open-label, single-arm, multicentre trial to receive enfuvirtide 90 mg bd and an optimised background regimen guided by a genotype. NRTI drugs were excluded, except for tenofovir. The primary endpoint was mean change from baseline in plasma HIV viral load at 48 weeks.   At entry, mean age was 47 years, 97% were male, 58% were CDC-C. Mean number of prior ARVs was 12 with a mean duration of 9 years. Mean CD4+ cell count was 242 cells/μL, mean HIV viral load was 4.5 log copies/mL (8% of patients had viral loads < 400), lipodystrophy was reported in 66% of patients. 34% reported neuropathy. 85% of patients used tenofovir during the study. 32% recommenced NRTIs during the study, due to unsatisfactory treatment outcomes, principally for treatment failure. At week 48 change from baseline HIV plasma viral load was −1.49 log10 copies/mL (p=0.0001) and 60% of patients had an HIV plasma viral load < 400 copies/mL (p=0.001). The mean increase in CD4+ cell count was 45 cells/μL (p=0.059). During the study total body lean and fat mass increased significantly by 1.25 Kg (p=0.01) and 1.6 Kg (p=0.001) respectively. Fasting lipids and glycemics were unchanged. 52 (88%) of patients were still taking ENF at week 48; two patients discontinued ENF due to hypersensitivity reactions.   Significant elevations in total lean & fat mass were observed for the trunk, arms and body as a whole after 48 weeks. The improvements may be small but significant in both central & peripheral compartments.   CHANGES FROM BASELINE TO WEWEK 48 FOR DEXA MEASUREMENTS Total fat changes (n=59)   Baseline Change at Wk 48 p ARMS Mass (g): 1214 176 0.0023 %: 14.9 1.5 0.0025 LEGS Mass (g): 2807 153 0.1785 %: 12.8 0.9 0.0143 TRUNK Mass (g): 8433 1099 0.0003 %: 22.0 1.5 0.0163 BODY Mass (g): 13085 1423 0.0012 %: 18.1 1.4 0.0046 Lean mass changes (n=59) ARMS Mass (g): 6460 135 0.0562 LEGS Mass (g): 17836 -177 0.3496 TRUNK Mass (g): 27524 1119 0.0026 BODY Mass (g): 55356 1152 0.0142   The authors concluded that the strategy of an NRTI sparing regimen plus enfuvirtide provided significant viral suppression and immunologic recovery at week 48 with concomitant improvements in both lean and fat mass.