Elvucitabine (ELV) is a nucleoside analogue from Achillion Pharmaceuticals that shows potent activity against HIV. Although ELV demonstrates bone toxicity when used at doses >/= 50mg/day, pharmacokinetic modeling suggests that at lower doses, ELV would continue to show potent anti-HIV activity, but also would be non toxic to bone marrow.

The aim of the current study, presented in a late breaker session by Dr. P. Collucci, was to validate the modeling study results and to reveal other aspects of ELV clinical pharmacology.

In this 21-day study, 24 HIV positive study participants received ELV 5 or 10mg qd or 20mg q48h for 21 days with concomitant Kaletra (400mg lopinavir/100mg ritonavir, q12h) treatment.

Results

ELV was effective and non-toxic at the doses used.

HIV RNA copies decreased 1.8, 1.9 and 2.0 log₁₀ for the 5mg qd, 10 mg qd and 20 q48h cohorts at day 21 vs. baseline.

Due to the long ELV T˝, Kaletra was continued to day 35 for the 2 higher doses.

ELV concentrations at Day 28 were 3X above the IC₅₀.

The continued activity 7 days after stoppage of ELV supports less frequent dosing (qw & biw) suggested by the modeling.

There was a trend toward a greater efficacy of the 20 mg q48h cohort,

No pts experienced safety issues or emergence of resistance.

These results suggest that ELV is safe and efficacious. The pharmacology of the drug suggests that it may present a better barrier to the development of resistance than other antiretroviral drugs. The data show that ELV is less affected by adherence issues.

The authors conclude that ELV should be further evaluated using less frequent dosing regimens.

01/10/05

Reference
P Colucci and others. The different clinical pharmacology of elvucitabine (beta-L-Fd4C) enables the drug to be given in a safe and effective manner with innovative drug dosing. Abstract LB-27. Abstracts of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. December 16-19, 2005. Washington, DC.

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