Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes

OBJECTIVE:To determine the antiretroviral activity of the integrase strand transfer inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), cabotegravir (CAB) and bictegravir (BIC), against different subtypes as well as primary and acquired drug resistance mutations (DRMs) in a patient-cohort infected with diverse subtypes. DESIGN:Biochemical and virological drug sensitivity analyses using patient-derived HIV type 1 (HIV-1) genes and cross-sectional/longitudinal clinical study. METHODS:Assays for 50% inhibition of 3′-end processing (IC50-3EP), strand transfer (IC50-ST) and drug sensitivity for five INSTIs were done using patient-derived integrase or gag-pol genes from subtypes A1, B, C, 01_AE and 02_AG. Integrase from INSTI-naive (n = 270) and experienced (n = 96) patients were sequenced. RESULTS:RAL had higher IC50-ST than the other INSTIs for all subtypes. EVG had higher IC50-ST for HIV 1 subtype C (P