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: | Kathleen Squires, Susan H. Eshleman, Daniel Bettendorf, Scott M. Hammer, William Spreen, Stephanie Lustgarten, Christine E. Koval, Joseph J. Eron, Lisa M. Demeter, Victor DeGruttola, Bach-Yen Nguyen, Margaret A. Fischl |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Cyclopropanes Male Oncology medicine.medical_specialty Efavirenz Anti-HIV Agents HIV Infections Indinavir Article law.invention chemistry.chemical_compound Double-Blind Method Randomized controlled trial Abacavir law Internal medicine Drug Resistance Viral medicine Humans Pharmacology (medical) Aged business.industry HIV Protease Inhibitors Middle Aged Virology Dideoxynucleosides Benzoxazines CD4 Lymphocyte Count Regimen Treatment Outcome Infectious Diseases chemistry Alkynes Virologic response HIV-1 Drug Therapy Combination Female business Nucleoside HIV drug resistance medicine.drug |
| Zdroj: | HIV Clinical Trials. 9:11-25 |
| ISSN: | 1945-5771 1528-4336 |
| DOI: | 10.1310/hct0901-11 |
| Popis: | 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.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.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: | OpenAIRE |
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