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RESISTANCE ANALYSES OF BICTEGRAVIR/EMTRICITABINE/TENOFOVIR ALAFENAMIDE SWITCH STUDIES
Kristen Andreatta1, Madeleine Willkom1, Ross Martin1, Silvia Chang1, Hal Martin1, Hiba Graham1, Erin Quirk1, Kirsten L. White1
1Gilead Sciences, Inc, Foster City, CA, USA
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.