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Racivir Demonstrates Safety and Efficacy in Patients Harboring HIV with the M184V Mutation and <3 TAM
Pedro Cahn*1, N Sosa2, A Wiznia3, M Patel3, D Ward4, F Palella5, J Sierra-Madero6, D Wheeler7, E DeJesus8, M Otto9, and Racivir 201 Study Team
1Fndn Huesped, Buenos Aires, Argentina; 2Med Res Ctr, Panama City, Panama; 3Jacobi Med Ctr, Bronx, NY, US; 4Washington, DC, US; 5Northwestern University, Chicago, IL, USA; 6Inst Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 7CARE-ID, Annandale, MD, US; 8Orlando Immunology Ctr, FL, US; and 9Pharmasset, Inc, Princeton, NJ, US
Background: Racivir
(RCV) (±)-b-2’,3’-dideoxy-3’-thia-5-fluorocytosine
([±]-FTC), is a 50:50 mixture of enantiomers with
potent anti-HIV/hepatitis B virus (HBV) activity and an excellent in vitro and in vivo safety profile. In a previous phase I study, RCV at doses
of 200, 400, or 600 mg (once daily) in combination with stavudine
and efavirenz for 2 weeks demonstrated potent
antiviral activity in HIV-1-infected treatment-naïve male volunteers. The
purpose of the current study was to determine the activity of Racivir in patients infected with HIV containing the M184V
mutation.
Methods: Enrolled patients
were required to have virus possessing the M184V mutation and to be receiving lamivudine (3TC) as a component of their ART. We randomized
42 subjects to receive either RCV (n =
26) in place of 3TC or to continue with 3TC (n = 16) in a double-blind manner for 28 days. HIV viral loads and
genotypes were determined at baseline (mean = 4.1 log10) and
throughout the study. Subjects were allowed to continue RCV in an open-label
manner with or without optimized background for an additional 20 weeks, based
on their primary care physicians’ advice.
Results: After 28 days of
blinded treatment the mean viral load change was 0.13 log10 in the 3TC
group and –0.4 log10 in the RCV group (p = 0.0004). A subset analysis of the RCV-treated group revealed
that the change in viral load was largely due to a positive antiviral response
in subjects who had a mutation pattern that included M184V and <3 thymidine analog mutations (TAM) with or without non-nucleoside
reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) mutations. In
this subset (n = 14), the mean viral
load change was –0.7 log10 (p
= 0.0002) with 28% achieving <400 copies/mL. No
severe adverse effects attributed to therapy were noted in either group over
the 28 days. Open-label dosing continues
and safety data from 24 weeks will be presented.
Conclusions: Racivir
has demonstrated antiviral activity in patients harboring HIV with M184V and
<3 TAM. These patients have genotypes consistent with first-line therapy
failure and may be candidates for second-line treatment regimens that contain
RCV. Future studies will be designed to
explore this concept further.
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