Brief Report: Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Participants With Preexisting K65R/N in HIV-1 in Phase 2/3/3b Clinical Trials
Year: 2025
Type: article
Abstract: 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.
Institution: Gilead Sciences (United States)
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Gilead Sciences
OpenAlex ID: W4413055561