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

BACKGROUND

Preexisting HIV-1 drug resistance affects antiretroviral treatment options for people with HIV-1 (PWH). Prior studies have demonstrated safety and efficacy of bictegravir/emtricitabine/tenofovir (TFV) alafenamide [B/F/tenofovir alafenamide fumarate (TAF)] in PWH including in virologically suppressed (VS) individuals with M184V/I mutations in reverse transcriptase that confer resistance to emtricitabine. K65R/N mutations in reverse transcriptase are selected by and confer 2-3-fold reduced susceptibility to TFV or its prodrugs TFV disoproxil fumarate (TDF) and TFV alafenamide fumarate (TAF) in vitro.

SETTING

Limited clinical data are available regarding the impact of preexisting K65R/N on B/F/TAF regimen efficacy.

METHODS

Post hoc analysis evaluating virologic outcomes in VS individuals with preexisting K65R/N mutations documented by historical genotypes and/or baseline proviral DNA sequencing who received B/F/TAF in 6 Phase 2/3/3b clinical trials.

RESULTS

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% and 1.5%, with most 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.

CONCLUSIONS

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.