Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy

Abacavir (1592U89) is a nucleoside inhibitor of human immunodeficiency viru s (HIV) type 1 reverse transcriptase (RT), Resistance to abacavir was studi ed with abacavir alone and with abacavir in combination with other nucleosi de analogues in cell culture, in virus isolates from zidovudine/lamivudine clinical trials, and in the first dose-escalating 12-week clinical trial (C NA2001) to evaluate abacavir clinical potency. Abacavir alone in vitro sele cted for mutations at HIV RT codons K65R, L74V, Y115F, and M184V, However, abacavir combined with zidovudine selected against virus with the M184V mut ation. Abacavir therapy in vivo resulted in Large decreases in HIV load (>1 log), even in 1 subject who had the M184V mutation at baseline, A total of 51% of subjects showed new mutations at any of codons K65R, L74V, and M184 V after abacavir monotherapy, compared with 11% who received zidovudine/aba cavir, Small changes (2- to 4-fold) in abacavir susceptibility were detecte d. On stopping therapy, reselection of the pretherapy sequence occurred wit hin 4 weeks.