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.