793
24-Week Data from Study AVX-201: A Prospective, Randomized, Double-blind, Dose-ranging Phase IIb Study of Apricitabine in Treatment-experienced Patients with M184V and NRTI Resistance
Pedro Cahn*1, J Altclas2, M Martins3, M Losso4, I Cassetti5, S Cox6, D Cooper7, and the AVX-201 study group
1Fndn Huesped, Buenos Aires, Argentina; 2Sanatorio de la Trinidad Mitre, Buenos Aires, Argentina; 3Inst Oulton, Cordoba, Argentina; 4Hosp JM Ramos Mejia, Buenos Aires, Argentina; 5Helios Salud, Buenos Aires, Argentina; 6Avexa Ltd, Melbourne, Australia; and 7Natl Ctr for HIV Epidemiology and Clin Res, Univ of New South Wales, Australia
Background: Apricitabine
(ATC) is a novel cytidine analogue which has shown potent reductions in viral
load during monotherapy in both treatment-naive and -experienced HIV-1-infected
patients. AVX-201 is a phase IIb study of apricitabine (ATC) compared to lamivudine
(3TC) with optimised background (from day 21) in treatment-experienced patients
with M184V.
Methods: We randomized 50 patients
failing therapy containing 3TC with confirmed M184V to receive 600 mg ATC, 800 mg
ATC, or 150 mg 3TC twice daily. At baseline, 52% had ≥3 thymidine
analogue mutations (TAM) and 76% had ≥1 NNRTI mutation. Background ART
was optimized on day 21 according to genotype: more than 40% introduced a protease
inhibitor (PI); 24% introduced darunavir (DRV) or tipranavir (TPV); 18%
introduced enfuvirtide (T-20). Of the total, 2
patients in 600-mg ATC arm did not optimize. Patients continued on optimized
background regimen (OBR) + ATC (600 mg or 800 mg) or 3TC until week
24, when all patients received open label ATC. The change in viral load at day
21 was the primary endpoint; in addition a further analysis was planned at week
24.
Results: ATC showed a –0.71 to –0.9
log reduction in viral load at day 21 (the primary endpoint) compared to 3TC (p
≤0.05; ANCOVA). At week 24 final results were:
|
Week 24 PP population
|
600 mg Twice-daily ATC
(n = 14)
|
800 mg Twice-daily ATC
(n = 15)
|
150 mg Twice-daily 3TC
(n = 12)
|
|
% <400 copies/mL
|
85.7
|
80
|
66.7
|
|
% <50 copies/mL
|
71.4
|
73.3
|
58.3
|
|
Δ CD4 cells/μL
|
+145.5
|
+211.5
|
+113.6
|
|
% ≥1log reduction in viral load
|
85.7
|
86.7
|
75
|
|
# severe adverse events
|
5
|
7
|
12
|
|
# severe adverse events
|
0
|
0
|
5
|
|
# related adverse events
|
3
|
5
|
5
|
These changes did not reach statistical
significance as the study was powered for the primary endpoint at day 21.
Conclusions: ATC
600 mg or 800 mg twice daily was safe and well tolerated over 24 weeks together
with OBR. At week 24, there was evidence of additional antiviral activity and
increased CD4 cells for both doses of ATC compared to 3TC. Larger phase IIb/III
trials of ATC in experienced patients are planned.
|
