Premium
Antiviral activity of apricitabine in treatment‐experienced HIV‐1‐infected patients with M184V who are failing combination therapy
Author(s) -
Cahn P,
Altclas J,
Martins M,
Losso M,
Cassetti I,
Cooper DA,
Cox S
Publication year - 2011
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2010.00887.x
Subject(s) - medicine , human immunodeficiency virus (hiv) , antiretroviral therapy , resistance mutation , antiviral therapy , virology , viral load , virus , reverse transcriptase , rna , biochemistry , gene , chemistry , chronic hepatitis
Objectives Apricitabine (ATC) is a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor (NRTI) with significant antiviral activity in vitro , including activity against HIV‐1 with reverse transcriptase mutations that confer resistance to other NRTIs. ATC has shown promising antiviral activity and good tolerability when given as monotherapy for 10 days in treatment‐naïve HIV‐1‐infected patients. Methods In this Phase II randomized, double‐blind study, 51 treatment‐experienced HIV‐1‐infected patients with the reverse transcriptase mutation M184V who were failing therapy which included lamivudine (3TC) were randomized to receive twice‐daily 600 mg ATC, 800 mg ATC or 150 mg 3TC for 21 days. Patients remained on their existing background regimen until day 21, when background therapy could be optimized according to genotype at screening. Results At day 21, the mean change in viral load was −0.71 and −0.90 log 10 HIV‐1 RNA copies/mL in the 600 and 800 mg ATC groups, respectively, compared with a −0.03 log 10 change in the 3TC group. In patients with at least three thymidine analogue mutations (TAMs) at baseline, greater reductions in viral load were observed in the 800 mg ATC group at day 21 than in the 600 mg ATC group. Few genotypic changes were detected at day 21 [two patients (600 mg ATC) lost and three patients (800 mg ATC) gained a TAM] and all patients with detectable virus retained the M184V mutation. The safety profiles of the two ATC doses were similar to that of 3TC. Conclusions Over the 21‐day treatment period, ATC showed promising antiviral activity and was well tolerated in treatment‐experienced patients with M184V, with or without additional TAMs.