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Prediction of HIV-1 Coreceptor Usage (Tropism) by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359
Richard H Haubrich1, Hongyu Jiang, Ronald Swanstrom
1University of California San Diego, San Diego, California 92103, USA. rhaubrich@ucsd.edu
HIV Clinical Trials
|May 18, 2007
Summary
Defining hypersusceptibility (HS) cut-points for non-nucleoside reverse transcriptase inhibitors (NNRTIs) like delavirdine (DLV) is crucial. This study identified a DLV HS fold change cut-point of 0.3-0.4, improving understanding of virologic response.
Area of Science:
- Virology
- Pharmacology
- Clinical Medicine
Background:
- Non-nucleoside reverse transcriptase inhibitor (NNRTI) hypersusceptibility (HS) is linked to improved virologic outcomes.
- Establishing precise phenotypic susceptibility cut-points for NNRTIs remains a challenge.
Purpose of the Study:
- To define phenotypic susceptibility cut-points for delavirdine (DLV) hypersusceptibility.
- To correlate these cut-points with virologic response in NNRTI-naive patients.
Main Methods:
- Phenotypic drug susceptibility testing (fold change in IC50) was performed on 96 antiretroviral-experienced, NNRTI-naive patients.
- Weighted fold change scores and regression models were used to determine baseline DLV HS cut-points.
- Classification and regression tree (CART) analysis was employed to identify predictive cut-points.
Main Results:
- Delavirdine (DLV) hypersusceptibility was present in 36% of patients at baseline.
- Analytic methods consistently identified DLV HS fold change cut-points between 0.3 and 0.4.
- A baseline DLV fold change less than 0.44 predicted week 4 virologic response.
Conclusions:
- A delavirdine (DLV) hypersusceptibility fold change cut-point of 0.3-0.4 was identified using multiple analytical methods.
- Early virologic responses are valuable for refining phenotypic cut-points, particularly for drugs with low genetic barriers.
- These findings aid in optimizing NNRTI treatment strategies based on phenotypic susceptibility.
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