Early Virologic Failure and Rescue Therapy of Tenofovir, Abacavir, and Lamivudine for Initial Treatment of HIV-1 Infection: TONUS Study

Abstract

Background: To assess the efficacy and safety of the triple NRTI combination of abacavir (ABC), lamivudine (3TC), and tenofovir (TDF) in a once-daily regimen. Method: 38 HIV-naive patients (pts) were treated in a prospective open-arm study over 48 weeks (W48). Virological failure was defined as never achieving plasma HIV-1 RNA <400 copies/mL or rebound of ≥0.7 log₁₀. Results: 12/36 (33%) pts had virologic failure at W24 and 10 additional pts had HIV RNA >50 copies/mL at W12 or W24. There was a significant association between baseline viral load (VL) and virologic failure in 0%, 29%, and 64% pts with baseline VL levels <4, 4-5, and >5 log₁₀ copies/mL, respectively (p = .014). 76% of pts developed K65R and M184V/I mutations by W24, and 19% developed M184V/I alone. At W4, 86% of pts had adequate plasma C_min for the 3 drugs. 14 pts with K65R and M184V/I were given a rescue therapy with a successful outcome (<50 copies/mL; median follow-up 48 weeks). Conclusion: Convergent genetic pathway to resistance, in conjunction with lower antiretroviral potency, may explain the high rate of selection K65R and M184V mutations. These mutations did not appear to have a negative effect on rescue therapy with a variety of regimens.

Keywords:

• abacavir
• antiretroviral therapy
• K65R mutations
• naive patients
• NRTIs regimen
• tenofovir