Comparison of predicted susceptibility between genotype and virtual phenotype HIV drug resistance interpretation systems among treatment-naive HIV-infected patients in Asia: TASER-M cohort analysis

BACKGROUND: Accurate interpretation of HIV drug resistance (HIVDR) testing is challenging, yet important for patient care. We compared genotyping interpretation, based on the Stanford University HIV Drug Resistance Database (Stanford HIVdb), and virtual phenotyping, based on the Janssen Diagnostics BVBA’s vircoTYPE™ HIV-1, and investigated their level of agreement in antiretroviral (ARV) naive patients in Asia, where non-B subtypes predominate. METHODS: Sequences from 1301 ARV-naive patients enrolled in the TREAT Asia Studies to Evaluate Resistance – Monitoring Study (TASER-M) were analysed by both interpreting systems. Interpretations from both Stanford HIVdb and vircoTYPE™ HIV-1 were initially grouped into 2 levels: susceptible and non-susceptible. Discrepancy was defined as a discordant result between the susceptible and non-susceptible interpretations from the two systems for the same ARV. Further analysis was performed when interpretations from both systems were categorised into 3 levels: susceptible, intermediate and resistant; whereby discrepancies could be categorised as major discrepancies and minor discrepancies. Major discrepancy was defined as having a susceptible result from one system and resistant from the other. Minor discrepancy corresponded to having an intermediate interpretation in one system, with a susceptible or resistant result in the other. The level of agreement was analysed using the prevalence adjusted bias adjusted kappa (PABAK). RESULTS: Overall, the agreement was high, with each ARV being in “almost perfect agreement”, using Landis and Koch’s categorisation. Highest discordance was observed for efavirenz (75/1301, 5.8%), all arising from susceptible Stanford HIVdb versus non-susceptible vircoTYPE™ HIV-1 predictions. Protease Inhibitors had highest level of concordance with PABAKs all above 0.99, followed by Nucleoside Reverse Transcriptase Inhibitors with PABAKs above 0.97 and non-NRTIs with the lowest PABAK of 0.88. The 68/75 patients with discordant efavirenz results harboured the V179D/E mutations compared to 7/1226 with no efavirenz discrepancy (p-value <0.001). In the 3-level comparison, all but one of the discrepancies was minor. CONCLUSIONS: The two systems agreed well with lowest concordance observed for efavirenz. When interpreting HIVDR, especially in non-B subtypes, clinical correlation is crucial, in particular when efavirenz resistance is interpreted based on V179D/E.