[LbOr19B] Enfuvirtide (T-20) in combination with an optimized background (OB) regimen vs. OB alone in patients with prior experience or resistance to each of the three classes of approved antiretrovirals (ARVs) in North America and Brazil.

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Enfuvirtide (T-20) in combination with an optimized background (OB) regimen vs. OB alone in patients with prior experience or resistance to each of the three classes of approved antiretrovirals (ARVs) in North America and Brazil.

[AUTHOR(S):] K Henry¹, J Lalezari², M OHearn³, B Trottier⁴, J Montaner⁵, P Piliero⁶, S Walmsley⁷, J Chung⁸, L Fang⁹

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr19B

BACKGROUND: Enfuvirtide (T-20; ENF) is an HIV fusion inhibitor, a new class of investigational ARV that blocks gp41-mediated fusion of HIV-1 to the host cell. TORO 1 (T-20 vs Optimized Regimen Only) is one of two Phase III studies of enfuvirtide, and is similar in design to TORO 2 performed in Europe and Australia.

METHODS: Patients from 49 sites in the USA, Canada, Mexico and Brazil with > 6 months prior experience with 3 classes of ARVs, and HIV-1 RNA > 5,000 copies/mL selected an OB regimen of 3-5 ARVs based on prior history and baseline (BL) genotypic (GT) and phenotypic (PT) viral resistance. Patients were randomized 2:1 to enfuvirtide (90 mg SC BID) + OB or OB alone

RESULTS: 491 patients were randomized, received at least one dose of study drug and had at least one post-BL assessment. Median BL HIV-1 RNA in both arms was 5.2 log₁₀ copies/mL, and overall CD4 count 80 cells/mm³. BL demographics and prior ARV experience were balanced across treatments; patients had prior experience with an average of 12 ARVs with over 80% of patients having virus with 5 or more primary mutations to the 3 ARV classes. Patients in both arms used an average of 4 ARVs in their OB regimen. At the 24 week primary analysis (ITT, Last Observation Carried Forward) the least squared means of change from BL in viral load (covariate, phenotypic sensitivity score) were -1.697 log₁₀ copies/mL for enfuvirtide + OB, and -0.763 log₁₀ copies/mL for OB alone, a difference of 0.934 log₁₀ copies/mL (p<0.0001). By 24 weeks 11.3% and 10.9% of patients discontinued from enfuvirtide + OB and OB respectively. Injection site reactions (ISRs) were experienced by 98% of patients but only 2.8% discontinued for these. Aside from ISRs, the safety profile was comparable across treatments and similar to previous Phase II studies.

CONCLUSIONS: Enfuvirtide provided significant viral suppression through 24 weeks when used with an OB regimen of oral ARVs in heavily pre-treated patients.

Presenting author: K Henry

020707
LbOr19B