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

被引:113
作者
Harrigan, PR [1 ]
Stone, C [1 ]
Griffin, P [1 ]
Nájera, I [1 ]
Bloor, S [1 ]
Kemp, S [1 ]
Tisdale, M [1 ]
Larder, B [1 ]
机构
[1] Glaxo Wellcome Res & Dev Ltd, Clin Virol & Surrogates Unit, Stevenage SG1 2NY, Herts, England
关键词
D O I
10.1086/315317
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Abacavir (1592U89) is a nucleoside inhibitor of human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT), Resistance to abacavir was studied with abacavir alone and with abacavir in combination with other nucleoside analogues in cell culture, in virus isolates from zidovudine/lamivudine clinical trials, and in the first dose-escalating 12-week clinical trial (CNA2001) to evaluate abacavir clinical potency. Abacavir alone in vitro selected for mutations at HIV RT codons K65R, L74V, Y115F, and M184V, However, abacavir combined with zidovudine selected against virus with the M184V mutation. 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 M184V after abacavir monotherapy, compared with 11% who received zidovudine/abacavir, Small changes (2- to 4-fold) in abacavir susceptibility were detected. On stopping therapy, reselection of the pretherapy sequence occurred within 4 weeks.
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页码:912 / 920
页数:9
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