Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

Genotype-Phenotype Regression Analysis

Last updated on 2023-5-1

Regression coefficients of the least-squares regression (LSR) model for predicting changes in INI susceptibility using genotypic predictors. INI mutations scored by HIVDB drug resistance interpretation system were included as explanatory variables and log fold change in susceptibility was the response variable. Ten repetitions of 5-fold cross-validation were performed to estimate the variance among the fitted coefficients.

The mutations shown are those that occurred at least 2 times in the genotype-phenotype dataset. For each mutation, the y axis indicates the magnitude of the mean coefficient of 50 LSR runs (10*5-fold cross-validation), and the error bar indicates the standard deviation from the mean. Positive coefficients indicate mutations that decrease drug susceptibility. Negative coefficients indicate mutations that increase drug susceptibility. Bars representing coefficients whose cross-validated means >= 3 standard deviations from zero are blue; other coefficient bars are white, indicating a lack of statistical significance after cross-validation.

The genotype-phenotype correlation dataset contained 809 isolates on which in vitro susceptibility tests were performed using the PhenoSense assay (Monogram, South San Francisco, USA): RAL (raltegravir; n=769), EVG (elvitegravir; n=711), DTG (dolutegravir; n=378), BIC (bictegravir, n=222). Too few in vitro susceptibilty data on cabotegravir using PhenoSense assay was available to be included in the model (Rhee et al. 2022).

Viruses with sequences containing mixtures at the major drug resistance mutation positions had been excluded because the presence of mixtures at these positions may confound genotype-phenotype correlations (n=46). Additionally redundant viruses obtained from the same individual that contained the same pattern of major drug resistance mutations had been excluded to minimize bias that would result from over-representing highly similar viruses (n=278).