Determination of clinically relevant cutoffs for HIV-1 phenotypic resistance estimates through a combined analysis of clinical trial and cohort data

2008 | JAIDS Journal of Acquired Immune Deficiency Syndromes

http://www.ncbi.nlm.nih.gov/pubmed/18360290

Abstract:

BACKGROUND: Clinically relevant cutoffs are needed for the interpretation of HIV-1 phenotypic resistance estimates as predicted by "virtual" phenotype HIV resistance analysis. METHODS: Using a clinical data set containing 2596 treatment change episodes in 2217 patients in 8 clinical trials and 2 population-based cohorts, drug-specific linear regression models were developed to describe the relation between baseline characteristics (resistance, viral load, and treatment history), new treatment regimen selected, and 8-week virologic outcome. RESULTS: These models were used to derive clinical cutoffs (CCOs) for 6 nucleoside/nucleotide reverse transcriptase inhibitors (zidovudine, lamivudine, stavudine, didanosine, abacavir, and tenofovir), 3 unboosted protease inhibitors (PIs; indinavir, amprenavir, and nelfinavir), and 4 ritonavir-boosted PIs (indinavir/ritonavir, amprenavir/ritonavir, saquinavir/ritonavir, lopinavir/ritonavir). The CCOs were defined as the phenotypic resistance levels (fold change [FC]) associated with a 20% and 80% loss of predicted wild-type drug effect and depended on the drug-specific dynamic range of the assay. CONCLUSIONS: The proposed CCOs were better correlated with virologic response than were biological cutoffs and provide a relevant tool for estimating the resistance to antiretroviral drug combinations used in clinical practice. They can be applied to diverse patient populations and are based on a consistent methodologic approach to interpreting phenotypic drug resistance.

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Winters B

BC Centre for Excellence in HIV/AIDS

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Determination of clinically relevant cutoffs for HIV-1 phenotypic resistance estimates through a combined analysis of clinical trial and cohort data

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