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document
Association of efavirenz hypersusceptibility with virologic response in ACTG 368 , a randomized trial of abacavir ( ABC ) in combination with efavirenz ( EFV ) and indinavir ( IDV ) in HIV-infected subjects with prior nucleoside analog experience . PURPOSE To evaluate the association of efavirenz hypersusceptibility ( EFV-HS ) with clinical outcome in a double-blind , placebo-controlled , randomized trial of EFV plus indinavir ( EFV+IDV ) vs. EFV+IDV plus abacavir ( ABC ) in 283 nucleoside-experienced HIV-infected patients . METHOD AND RESULTS Rates of virologic failure were similar in the 2 arms at week 16 ( p = .509 ) . Treatment discontinuations were more common in the ABC arm ( p = .001 ) . Using logistic regression , there was no association between virologic failure and either baseline ABC resistance or regimen sensitivity score . Using 3 different genotypic scoring systems , EFV-HS was significantly associated with reduced virologic failure at week 16 , independent of treatment assignment . In some patients on the nucleoside-sparing arm , the nucleoside-resistance mutation L74V was selected for in combination with the uncommonly occurring EFV-resistance mutations K103N+L100I ; L74V was not detected as a minority variant , using clonal sequence analysis , when the nucleoside-sparing regimen was initiated . CONCLUSION Premature treatment discontinuations in the ABC arm and the presence of EFV-HS HIV variants in this patient population likely made it difficult to detect a benefit of adding ABC to EFV+IDV . In addition , L74V , when combined with K103N+L100I , may confer a selective advantage to the virus that is independent of its effects on nucleoside resistance .
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Intervention_Pharmacological
efavirenz
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Intervention_Pharmacological
ACTG 368
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Intervention_Pharmacological
abacavir ( ABC )
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Intervention_Pharmacological
efavirenz ( EFV )
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Intervention_Pharmacological
indinavir ( IDV
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
EFV plus indinavir ( EFV+IDV ) vs. EFV+IDV plus abacavir ( ABC )
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Intervention_Pharmacological
EFV-HS
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Intervention_Pharmacological
EFV-HS HIV
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Intervention_Pharmacological
EFV+IDV
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Outcome_Other
Rates of virologic failure
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Outcome_Other
Treatment discontinuations
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Outcome_Other
virologic failure
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Outcome_Other
either
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Outcome_Mental
baseline ABC resistance
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Outcome_Other
or regimen sensitivity score
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Outcome_Mental
treatment discontinuations
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Outcome_Other
adding ABC to EFV+IDV
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Outcome_Adverse-effects
effects on nucleoside resistance
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Participant_Condition
HIV-infected
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Participant_Sample-size
283
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Participant_Condition
HIV-infected