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POOLED WEEK 48 EFFICACY AND BASELINE RESISTANCE: B/F/TAF IN TREATMENT-NAIVE PATIENTS
Kirsten L. White1, Rima Kulkarni1, Madeleine Willkom1, Ross Martin1, Silvia Chang1, Xuelian Wei1, William Garner1, Devi SenGupta1, Hal Martin1, Erin Quirk1, Andrew Cheng1
1Gilead Sciences, Inc, Foster City, CA, USA
Two phase 3, randomized, blinded, studies showed HIV-1 treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) had no emergent resistance and was non-inferior to abacavir/dolutegravir/lamivudine (ABC/DTG/3TC, Study 1489) and DTG+F/TAF (Study 1490) in treatment-naïve subjects. Here, pooled efficacy analyses through W48 and the effect of baseline resistance on treatment response are described.
Population sequencing of HIV-1 protease and reverse transcriptase was done at screening; resistance to study NRTIs was excluded. Baseline retrospective next generation sequencing of integrase (all randomized, N=1274) was correlated with prespecified pooled virologic outcomes from the 2 studies. Virologic failures with HIV-1 RNA ≥200 c/mL had resistance analyses at confirmed failure or last visit.
High levels of virologic suppression of HIV-1 RNA to <50 c/mL at W48 was achieved: 91% (576/634) in the pooled B/F/TAF groups and 93% of subjects in both the DTG/ABC/3TC (293/315) and DTG+F/TAF (302/325) groups, respectively. There was rapid suppression to HIV-1 RNA <50 c/mL at W4: 76% (477/625) in the B/F/TAF group, 76% (236/311) in the DTG/ABC/3TC group, and 80% (258/324) in the DTG+F/TAF group by the Missing=Excluded approach. HIV-1 subtype B was present in 89% of patients. 92% (1048/1138) B subtype and 90% (123/136) non-B subtype had HIV-1 RNA <50 c/mL at W48. Pre-existing primary resistance mutations (-R) to any drug class were found in 18% (224/1274) of patients overall and consisted of NRTI-R in 2%, NNRTI-R in 13.2%, PI-R in 2.9%, and INSTI-R in 1.3%. One subject in the B/F/TAF group had Q148H+G140S at baseline and was suppressed with HIV-1 RNA <50 c/mL at W48. HIV-1 RNA <50 c/mL at W48 was similar with or without pre-existing resistance mutations (92%; 205/224 vs 92%; 966/1050, respectively). Through W48, 17 patients qualified for resistance testing (1.3% (8/634) B/F/TAF; 1.3% (4/315) ABC/DTG/3TC; 1.5% (5/325) DTG+F/TAF); none had emergent resistance to study drugs.
Treatment with B/F/TAF, ABC/DTG/3TC, or DTG+F/TAF rapidly achieved and maintained high rates of virologic suppression in HIV-1 treatment-naïve subjects. The presence of pre-existing resistance mutations did not affect treatment outcomes. Development of primary drug resistance mutations to study drug was not observed through W48.