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

TitleNon-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359.
Publication TypeJournal Article
Year of Publication2007
AuthorsHaubrich RH, Jiang H, Swanstrom R, Bates M, Katzenstein D, Petch L, Fletcher CV, Fiscus SA, Gulick RM
Corporate AuthorsAIDS Clinical Trials Group Protocol 359 Team
JournalHIV Clin Trials
Volume8
Issue2
Pagination63-7
Date Published2007 Mar-Apr
ISSN1528-4336
KeywordsAnti-HIV Agents, Delavirdine, Drug Resistance, Viral, Female, HIV Infections, HIV-1, Humans, Inhibitory Concentration 50, Male, Microbial Sensitivity Tests, Regression Analysis, Reverse Transcriptase Inhibitors, RNA, Viral, Treatment Outcome, Viral Load
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.

DOI10.1310/hct0802-63
Alternate JournalHIV Clin Trials
PubMed ID17507321
Grant List200VC006 / / PHS HHS / United States
200VC009 / / PHS HHS / United States
5P30 AI36214 / AI / NIAID NIH HHS / United States
AI25868 / AI / NIAID NIH HHS / United States
AI27666 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI46386 / AI / NIAID NIH HHS / United States
AI50485 / AI / NIAID NIH HHS / United States
AI51966 / AI / NIAID NIH HHS / United States
AI68637 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
K24 AI064086-02 / AI / NIAID NIH HHS / United States
K24AI64086 / AI / NIAID NIH HHS / United States
M01RR00070 / RR / NCRR NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
P30 AI50410 / AI / NIAID NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States
RR00047 / RR / NCRR NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States