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48-wk resistance data comparing GW433908 boosted & unboosted with nelfinavir

Boston (Feb. 11, 2003) Forty-eight-week data were presented here today from two Phase III studies (NEAT and SOLO) of treatment-nave patients with HIV infection, evaluating the resistance profile of the investigational protease inhibitor (PI) GW433908 (908) dosed twice a day (BID) or 908 boosted with the PI ritonavir (908/r) dosed once a day (QD) compared to the PI nelfinavir (NFV) BID. The medications in both studies were administered as part of combination therapy that also included 300 mg abacavir (ABC) BID and 150 mg lamivudine (3TC) BID. ABC and 3TC are nucleoside reverse transcriptase inhibitors (NRTIs).

908 is the calcium phosphate ester pro-drug of amprenavir (APV) and was co-discovered by GlaxoSmithKline (GSK) and Vertex Pharmaceuticals (Nasdaq: VRTX). In the SOLO study, no patients (0 percent) in the 908/r arm, out of 32 subjects experiencing virologic failure or with ongoing viral replication, had detectable primary or secondary PI mutations. In contrast, 27 of 54 patients (50 percent) in the NFV arm developed primary or secondary PI mutations. The clinical relevance of the resistance data is currently under evaluation.

In the NEAT study, 5 of 29 patients (17 percent) who experienced treatment failure in the unboosted 908 arm had mutations characteristic of APV resistance. NFV-selected mutations were observed in 7 of 26 patients (27 percent) who experienced virologic failure in the nelfinavir arm.

In the NEAT study, mutations selected by 908 were consistent with the spectrum of mutations selected by APV. Mutations detected in patients taking unboosted 908 included I54L/M, M46I and V32I+I47V. Mutations observed with other PIs (D30N, I54V, V82A/T/S, L90M) were not detected among patients taking unboosted 908.

In the SOLO study, there was a statistically significant difference between 908/r QD and NFV BID in the incidence of treatment emergent mutations selected by either the study PI (P<0.001) or the NRTIs ABC and
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Contact: Amy Kling
akling@pcipr.com
312-558-1770
Public Communications Inc.
11-Feb-2003


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