The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients : results from a randomized, double-blind, trial

Objective: To compare the antiviral activity of abacavir (ABC) with stable background therapy (SBG) and SBG alone in antiretroviral therapy-experienced subjects as demonstrated by the proportion of subjects with plasma HIV-1 RNA less than or equal to 400 copies/ml, plasma HIV-1 RNA and CD4 cell count profiles, and safety and tolerance of the two regimens over 16 weeks. Design: One-hundred and eighty-five HIV-1 infected adults, with CD4 cell counts greater than or equal to 100 x 10 super(6)/l and plasma HIV-1 RNA of 400-50 000 copies/ml and who had received SBG therapy for at least 12 weeks, were randomized to receive ABC (300 mg twice daily) or placebo in a double blind, multi-centre study. Methods: Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4 cell counts. Genotypic and phenotypic resistance was determined at baseline and week 16. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses. Results: At week 16 significantly more subjects receiving ABC + SBG had plasma HIV-1 RNA less than or equal to 400 copies/ml (36/92, 39%) than subjects receiving SBG alone (7/93, 8%; P < 0.001). A similar response was observed in both the lamivudine naive and lamivudine-experienced subjects. The presence of the M184V mutation did not preclude an antiviral response to ABC; 73% of subjects with the M184V mutation alone experienced a greater than or equal to 1.0 log sub(10) copies/ml reduction in plasma HIV-1 RNA or had a value of less than or equal to 400 copies/ml by week 16. Conclusions: ABC was generally well tolerated and exerted significant antiviral effect when added to combination antiretroviral therapy over 16 weeks.