Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. Academic Article uri icon

Overview

abstract

  • PURPOSE: Non-nucleoside reverse transcriptase inhibitor (NNRTI) hypersusceptibility (HS) improves virologic response to those agents, but phenotypic susceptibility cut-points, and methods to determine the cut-points, have not been completely defined. METHOD: Phenotypic drug susceptibility (fold change in IC50 [FC]) was determined for 96 randomly selected antiretroviral-experienced, NNRTI-naive patients who received a delavirdine (DLV)-containing regimen in ACTG 359. A weighted FC score was used to account for other regimen agents. Regression models were used to define baseline DLV HS cut-points using week 4 or week 16 responses. RESULTS: At study entry, DLV HS was present in 36% (35/96) of patients. Models explored HS cut-points from 0.2-1.0 using the week 4 virologic response. Using either a binary or continuous endpoint, DLV HS cut-points between 0.3 and 0.4 were identified. The classification and regression tree (CART) analysis identified baseline DLV FC <0.44 as a predictor of week 4 response. CONCLUSIONS: In relating drug HS to virologic response, several different analytic methods identified a DLV HS FC cut-point of 0.3-0.4. In refining phenotypic cut-points, early virologic responses (not confounded by rebound) may be better metrics than later responses, especially for drugs with low genetic barriers, such as DLV.

publication date

  • January 1, 2007

Research

keywords

  • Anti-HIV Agents
  • Delavirdine
  • Drug Resistance, Viral
  • HIV-1
  • Reverse Transcriptase Inhibitors

Identity

Scopus Document Identifier

  • 34250706943

Digital Object Identifier (DOI)

  • 10.1310/hct0802-63

PubMed ID

  • 17507321

Additional Document Info

volume

  • 8

issue

  • 2