HIV and Hepatitis.com Coverage of the
14th Annual Conference on Retroviruses
and Opportunistic Infections (14th CROI)
February 25 - 28, 2007, Los Angeles, CA

Racivir Demonstrates Good Safety and Efficacy in Patients with NRTI-resistant HIV

Racivir is a novel nucleoside reverse transcriptase inhibitor (NRTI) being developed by Pharmasset. A cytosine analog like 3TC (lamivudine; Epivir) and emtricitabine (FTC; Emtriva), racivir is also active against both HIV and hepatitis B virus (HBV).

Studies to date have shown that racivir has a favorable safety profile, both in vitro and in vivo. In a previous Phase I study, racivir at doses of 200, 400, or 600 mg once daily in combination with d4T (Zerit) and efavirenz (Sustiva) demonstrated potent antiviral activity over 2 weeks in HIV positive, treatment-naive subjects.

The current study, reported at the 14th Conference on Retroviruses and Opportunistic Infections in February, assessed the activity of racivir in patients with HIV containing the M184V mutation, which confers resistance to 3TC and emtricitabine. All 42 participants were on 3TC-containing regimens at study entry; 26 switched from 3TC to racivir, while 16 stayed on 3TC. The study period lasted 28 days, but subjects could continue on open-label racivir for an additional 20 weeks.
Results

• After 28 days, the mean HIV RNA level fell by 0.4 log10 in the racivir group, while rising by 0.13 log10 in the 3TC continuation arm.

• A subgroup analysis revealed that the difference was largely due to virological response in patients who had the M184V mutation plus fewer than 3 thymidine analog mutations (TAMs), with or without NNRTI- or PI-resistance mutations.

• In this subgroup of 14 subjects, HIV RNA decreased by a mean 0.7 log10, and 28% achieved viral loads below 400 copies/mL.

• Patients who achieved undetectable viral loads maintained virological suppression during the open-label phase.

• No severe adverse effects attributed to therapy were noted in either arm.

Conclusion

"Racivir has demonstrated antiviral activity in patients harboring HIV with M184V and < 3 TAM[s]," the researchers concluded. "These patients have genotypes consistent with first-line therapy failure and may be candidates for second-line treatment regimens that contain racivir."
They added that future studies are planned to further explore this strategy.

Link to study abstract

Fndn Huesped, Buenos Aires, Argentina; Med Res Ctr, Panama City, Panama; Jacobi Med Ctr, Bronx, NY; Northwestern University, Chicago, IL; Inst Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; CARE-ID, Annandale, MD; Orlando Immunology Ctr, FL; Pharmasset, Inc, Princeton, NJ.

04/03/07

Reference

P Cahn, N Sosa, A Wiznia, and others (Racivir 201 Study Team). Racivir Demonstrates Safety and Efficacy in Patients Harboring HIV with the M184V Mutation and < 3 TAM. 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, California. Abstract 488 (poster).











































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