Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Participants with Preexisting K65R/N in HIV-1 in Phase 2/3/3b Clinical Trials.

Preexisting HIV-1 drug resistance impacts antiretroviral treatment options for people with HIV-1 (PWH). Prior studies have demonstrated safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in PWH including in virologically suppressed individuals with M184V/I mutations in reverse transcriptase (RT) which confer resistance to emtricitabine. K65R/N mutations in RT are selected by and confers 2-3-fold reduced susceptibility to tenofovir (TFV) or its prodrugs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) in vitro. Limited clinical data are available regarding the impact of preexisting K65R/N on B/F/TAF regimen efficacy. Post hoc analysis evaluating virologic outcomes in individuals virologically suppressed (VS) with preexisting K65R/N mutations documented by historical genotypes and/or baseline proviral DNA sequencing who received B/F/TAF in six Phase 2/3/3b clinical trials. Preexisting K65R/N mutations were detected in 20 of 2028 VS participants who received B/F/TAF. Frequency of K65R/N in the 6 studies ranged between 0% - 1.5%, with the majority of participants (95%; n=19/20) having K65R. Overall, K65R/N mutations were most commonly observed with other resistance associated mutations (70.0%, n=14/20), including M184V/I (45.0%, n=9/20), and ≥ 1 thymidine analog mutations (30.0%, n=6/20). All participants with preexisting K65R/N receiving B/F/TAF (n = 20/20) had virologic suppression (HIV-1 RNA < 50 copies/mL) through end of study, with no virologic failure or treatment-emergent resistance to B/F/TAF. Despite the presence of the TFV signature resistance mutation K65R/N, participants receiving B/F/TAF maintained virologic suppression demonstrating the efficacy of B/F/TAF in this population.