one more article from two well-credentialled ladsthink this...

one more article from two well-credentialled lads
think this thing may have some potential

JAC Advance Access published online on December 9, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp422

Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine

Pedro Cahn and Mark A. Wainberg

1 Fundacin Huesped, Angel Peluffo 3932, Buenos Aires C1202ABB, Argentina 2 McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, 3755 Cte-Ste-Catherine Road, Montreal, Quebec H3T 1E2, Canada

* Corresponding author. Tel: +5411-4981-7777; Fax: +5411-4982-4024; E-mail: [email protected]

Apricitabine is a novel deoxycytidine nucleoside reverse transcriptase inhibitor (NRTI) currently in clinical development for the treatment of HIV infection. Apricitabine shows antiviral activity in vitro against HIV-1 strains and clinical isolates with mutations in the reverse transcriptase that confer resistance to other NRTIs, including M184V, thymidine analogue mutations (TAMs), nucleoside-associated mutations such as L74V and certain mutations at codon 69. Apricitabine has shown activity in treatment-experienced HIV-1-infected patients with NRTI resistance (with M184V and up to five TAMs) as well as in treatment-naive patients. Resistance to apricitabine is slow to develop in vitro and there has been little evidence of development of resistance to apricitabine in clinical use thus far, including patients receiving apricitabine for up to 48 weeks. The resistance profile of apricitabine suggests there is a low potential for cross-resistance with the currently available NRTIs and, thus, apricitabine may provide a treatment option for treatment-experienced HIV-1-infected patients with resistance to other NRTIs. In particular, the activity of apricitabine in the presence of the M184V mutation, which confers high-level resistance to lamivudine and emtricitabine, lends it to being used as a replacement for deoxycytidine analogues in patients who have failed treatment with lamivudine or emtricitabine.