Comparative Analysis of Two Commercial Phenotypic Assays for Drug Susceptibility Testing of Human Immunodeficiency Virus Type 1

Abstract

Human immunodeficiency virus type 1 (HIV-1) isolates from 50 plasma specimens were analyzed for phenotypic susceptibility to licensed reverse transcriptase inhibitors and protease inhibitors by the Antivirogram and PhenoSense HIV assays. Twenty of these specimens were from recently seroconverted drug-naïve persons, and 30 were from patients who were the sources of occupational exposures to HIV-1; 16 of the specimens in the latter group were from drug-experienced patients. The phenotypic results of the Antivirogram and PhenoSense HIV assays were categorized as sensitive or reduced susceptibility on the basis of the cutoff values established by the manufacturers of each assay. Data for 12 to 15 drugs were available by both assays for 38 specimens and represented a total of 529 pairs of results. The two data sets had a 91.5% concordance by phenotypic category. The discordant results (n ‫؍‬ 45) were distributed randomly among 26 specimens and included 28 results (62.2%) which were within a twofold difference of the assay cutoff values. None of the discordant results were associated with primary resistance mutations that predicted high-level (>20-fold) resistance. Discordant results were distributed equally among specimens from drug-experienced and drugnaïve individuals and were slightly higher for protease inhibitors than for nonnucleoside reverse transcriptase inhibitors or nucleoside reverse transcriptase inhibitors. The findings of the present study demonstrate that the results of the Antivirogram and PhenoSense HIV assays correlate well, despite the use of different testing strategies.

Sensitive Deep-Sequencing-Based HIV-1 Genotyping Assay To Simultaneously Determine Susceptibility to Protease, Reverse Transcriptase, Integrase, and Maturation Inhibitors, as Well as HIV-1 Coreceptor Tropism

“…While there is usually high concordance between drug resistance methodologies (13,119,120), in general, population-based sequencing HIV-1 tropism tests are less sensitive and less specific than phenotypic assays (8,41). Here, DeepGen HIV identified all the drug resistance mutations detected by the standard population sequencing-based HIV-1 genotyping tests used to monitor 166 individuals in two well-established cohorts of patients.…”

“…A multitude of studies have compared the efficacies of phenotypic and genotypic assays to detect and quantify HIV-1 drug resistance (116)(117)(118)(119)(120) or coreceptor tropism (38,(121)(122)(123)(124). While there is usually high concordance between drug resistance methodologies (13,119,120), in general, population-based sequencing HIV-1 tropism tests are less sensitive and less specific than phenotypic assays (8,41).…”

Dose–response curve slope is a missing dimension in the analysis of HIV-1 drug resistance

“…Although the molecular mechanisms of resistance are well studied, the pharmacodynamics of resistance are less well understood. Resistance is typically measured as a change in IC 50 (Table S1) relative to WT virus (27)(28)(29)(30). Antiretroviral drugs are used at concentrations above IC 50 , however, and inhibition at clinical concentrations can only be predicted from IC 50 if the shape of the dose-response curve is known.…”

Novel Recombinant Virus Assay for Measuring Susceptibility of Human Immunodeficiency Virus Type 1 Group M Subtypes To Clinically Approved Drugs

“…Despite the use of different testing strategies, the available assays show good correlations, although care should be taken in extrapolating values near the cutoffs of the different formats (36,52). The addition of ENF and MVC to the existing range of drugs in clinical practice prompted the need for assays applicable to viruses capable of using either coreceptor.…”