The novel, unboosted integrase strand transfer inhibitor (INSTI) bictegravir (B) has been coformulated with the nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone emtricitabine (F)/tenofovir alafenamide (TAF). In 2 phase 3 clinical studies, stably suppressed HIV-1 infected adults who switched to B/F/TAF from regimens consisting of either a boosted protease inhibitor (PI) + 2 NRTIs (N=290; Study 1878) or the INSTI dolutegravir (DTG) + NRTIs abacavir (ABC)/lamivudine (3TC) (N=282; Study 1844) had low rates of virologic failure (VF; HIV-1 RNA ≥50 copies/mL by snapshot analysis) through week (W) 48, and switching was noninferior to comparator arms. Here, integrated resistance analyses are described.
Available historical plasma HIV-1 RNA genotypes and retrospective proviral DNA genotyping of baseline viral isolates were analyzed. Viral isolates from patients with HIV-1 RNA ≥200 copies/mL at confirmed VF, discontinuation, or W48 were analyzed for protease (PR), reverse transcriptase (RT), and integrase (IN) genotype and phenotype.
Of the 572 patients who switched to B/F/TAF, pretreatment historical genotypes and/or retrospective proviral DNA genotypes of baseline viral isolates were obtained from 394 patients for PR/RT and from 158 patients for IN. Preexisting primary INSTI resistance (-R), NRTI-R, nonnucleoside RT inhibitor (NNRTI)-R, and PI-R substitutions were observed in 0.6% (1/158), 14.0% (55/394), 18.3% (72/394), and 6.3% (25/394), respectively. Pre-switch resistance to F and/or TAF was retrospectively detected at baseline in 8.9% (35/394) of patients and consisted of K65N/R (n=5), M184V/I (n=30), and/or ≥3 thymidine analog mutations (TAMs) that include M41L or L210W (n=4) in RT. Overall, 1.4% (8/572) of B/F/TAF treated patients experienced VF through W48. Of the 35 patients with preexisting F/TAF resistance, 1 (2.9%) experienced VF due to nonadherence. Postbaseline resistance analyses were conducted on viral isolates from 5 patients in the B/F/TAF group and 7 patients in the comparator groups. No patients on B/F/TAF developed de novo resistance to study drugs. One patient on boosted darunavir + ABC/3TC developed a treatment-emergent L74V substitution in RT.
Low rates of virologic failure occurred among the 572 patients who switched to B/F/TAF, including the 35 with preexisting F/TAF resistance. Through W48 there was zero treatment-emergent resistance in B/F/TAF treated patients demonstrating the utility of B/F/TAF in HIV-1-suppressed patients.