 |
Superior activity of apricitabine compared to 3TC over 21 days in treatment experienced HIV-1 infected patients failing therapy with M184V and NRTI resistance
Presented by Pedro Cahn, Argentina.
Cahn P.1, Altclas J.2, Martins M.3, Losso M.4, Cassetti I.5, Cooper D.6
1Fundacion Huesped, Buenos Aires, Argentina, 2Sanatorio de la Trinidad Mitre, Buenos Aires, Argentina, 3Instituto Oulton, Cordoba, Argentina, 4Hospital J M Ramos Mejia, Buenos Aires, Argentina, 5Helios Salud, Buenos Aires, Argentina, 6St Vincent's Hospital Medical Centre, Sydney, Australia
Objectives: New well tolerated NRTIs are needed to overcome drug resistance and complement other new therapeutic approaches. Apricitabine (ATC) is a novel cytidine analogue in development for treatment of HIV infection which shows potent activity in treatment naïve patients, and is active in vitro against M184V ± other TAMs/NAMs. AVX-201 is a 48 week Phase IIb study to determine the efficacy of ATC in treatment experienced patients failing therapy with M184V and other TAMs/NAMs.
Methods: Patients failing therapy containing 3TC with confirmed M184V were randomised to 600mg ATC, 800mg ATC, or 150mg 3TC BID for 21 days. No other changes in the background ART were permitted. At day 21, background ART was optimized according to genotype. The primary endpoint was the change in HIV RNA from baseline to Day 21 compared to 3TC.
Results: Both ATC doses produced significant reductions in HIV-1 RNA at day 21 compared to 3TC. The 800mg dose may provide some additional activity compared to 600mg in patients with >2 TAMs. At Day 21, no new mutations developed and all patients with detectable virus retained M184V. The safety profile of both doses were indistinguishable from 3TC.
| Day 21 | 600mg ATC n=17 | 800mg ATC n=16 | 150mg 3TC n=14 | | Mean change in log10 HIV RNA | overall -0.9 (p=0.006) >2 TAMs -0.37 | overall -0.71 (p=0.0506) >2 TAMs -0.75 | overall -0.029 >2 TAMs 0.025 | | number with >0.5 log reduction | 10 (p=0.0005) | 7 (p=0.0073) | 0 | | number with >1 log reduction | 9 (p=0.0013) | 6 (p=0.0185) | 0 | | number with <400 copies/mL | 5 (p=0.0482) | 2 (p=0.4851) | 0 | | number with grade 3 and 4 AEs | 0 | 1 | 1 |
Conclusions: ATC provides clinically significant activity over 21 days functional monotherapy in treatment experienced patients with NRTI resistance, with no evidence of ATC resistance development, and an excellent safety profile. Based on these encouraging results, Phase III trials are planned to start shortly to confirm the activity and safety in the long term.
Back to the session -
Back to the Programme-at-a-Glance
|
|