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.
Autor: | Demeter LM; University of Rochester, Rochester, New York 14642, USA. lisa_demeter@urmc.rochester.edu, DeGruttola V, Lustgarten S, Bettendorf D, Fischl M, Eshleman S, Spreen W, Nguyen BY, Koval CE, Eron JJ, Hammer S, Squires K |
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Jazyk: | angličtina |
Zdroj: | HIV clinical trials [HIV Clin Trials] 2008 Jan-Feb; Vol. 9 (1), pp. 11-25. |
DOI: | 10.1310/hct0901-11 |
Abstrakt: | 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. |
Databáze: | MEDLINE |
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