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and Hepatitis.com Coverage of the
50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010)
New NRTI Festinavir Exhibits Good Anti-HIV Activity and Safety in Phase 1b/2a Study
Festinavir, chemically known as or 4'-ethynyl-d4T, was previously shown to have activity against wild-type and several NRTI- and NNRTI-resistant HIV strains in laboratory studies. It also appears to have prolonged activity, which might allow less frequent dosing.
Festinavir's chemical cousin, d4T, can cause serious side effects, including mitochondrial toxicity that may manifest as lipoatrophy (fat loss in the face and limbs), peripheral neuropathy, or liver damage. In cell cultures, however, festinavir appears to be less toxic, being a weaker inhibitor of mitochondrial DNA synthesis. The drug was previously found to be safe and well-tolerated up to 900 mg in a single oral dose given to healthy HIV negative volunteers.
In the poster presented at ICAAC, researchers described a double-blind, placebo-controlled, dose-escalating study of festinavir in 32 treatment-experienced HIV positive patients who were currently not taking antiretroviral drugs. At study entry participants had an average viral load of about 4.4 logs and a mean baseline CD4 count of about 400 cells/mm3.
Four cohorts of 8 patients each were sequentially recruited and received festinavir monotherapy at doses of 100, 200, 300, and 600 mg once-daily for 10 days; 2 participants in each cohort were randomly assigned to receive placebo.
CD4 cell count, and safety and tolerability parameters were assessed
at baseline and after receiving therapy. A 24-hour pharmacokinetic analysis
was done on days 1 and 10. HIV reverse transcriptase (RT) and protease
genotyping were performed at baseline, day 10, and day 17 to look for
drug resistance mutations.
monotherapy for 10 days appears safe and well-tolerated up to 600 mg/day
in HIV-infected, treatment-experienced patients," the investigators
concluded. "Antiviral efficacy appears remarkable for a nucleoside
[reverse transcriptase inhibitor] and deserves further studies."