Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359

Richard H. Haubrich, Hongyu Jiang, Ronald Swanstrom, Michael Bates, David Katzenstein, Leslie Anne Petch Lee, Courtney V. Fletcher, Susan A. Fiscus, Roy M. Gulick

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: Non-nucleoside reverse transcriptase inhibitor (NNRTI) hypersusceptibility (HS) improves virologic response to those agents, but phenotypic susceptibility cutpoints, 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.

Original languageEnglish (US)
Pages (from-to)63-67
Number of pages5
JournalHIV Clinical Trials
Volume8
Issue number2
DOIs
StatePublished - Mar 1 2007

Fingerprint

Delavirdine
Reverse Transcriptase Inhibitors
Pharmaceutical Preparations
Inhibitory Concentration 50
Regression Analysis

Keywords

  • Hypersusceptibility
  • Phenotype
  • Virologic response

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Haubrich, R. H., Jiang, H., Swanstrom, R., Bates, M., Katzenstein, D., Petch Lee, L. A., ... Gulick, R. M. (2007). Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. HIV Clinical Trials, 8(2), 63-67. https://doi.org/10.1310/hct0802-63

Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. / Haubrich, Richard H.; Jiang, Hongyu; Swanstrom, Ronald; Bates, Michael; Katzenstein, David; Petch Lee, Leslie Anne; Fletcher, Courtney V.; Fiscus, Susan A.; Gulick, Roy M.

In: HIV Clinical Trials, Vol. 8, No. 2, 01.03.2007, p. 63-67.

Research output: Contribution to journalArticle

Haubrich, RH, Jiang, H, Swanstrom, R, Bates, M, Katzenstein, D, Petch Lee, LA, Fletcher, CV, Fiscus, SA & Gulick, RM 2007, 'Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359', HIV Clinical Trials, vol. 8, no. 2, pp. 63-67. https://doi.org/10.1310/hct0802-63
Haubrich RH, Jiang H, Swanstrom R, Bates M, Katzenstein D, Petch Lee LA et al. Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. HIV Clinical Trials. 2007 Mar 1;8(2):63-67. https://doi.org/10.1310/hct0802-63
Haubrich, Richard H. ; Jiang, Hongyu ; Swanstrom, Ronald ; Bates, Michael ; Katzenstein, David ; Petch Lee, Leslie Anne ; Fletcher, Courtney V. ; Fiscus, Susan A. ; Gulick, Roy M. / Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. In: HIV Clinical Trials. 2007 ; Vol. 8, No. 2. pp. 63-67.
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