Background: Globally, most people living with HIV are infected with non-B subtype HIV-1. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a potent, once-daily, single tablet regimen for treatment of HIV-1 infection, with in vitro activity against all B and non-B subtypes. Here, we present an expanded analysis of B/F/TAF efficacy by HIV-1 subtype and pre-existing resistance mutations in treatment-naïve and virologically-suppressed switch study participants.
Methods: Participants from five Phase 3 B/F/TAF studies?GS-US-380-1489 and GS-US-380-1490 (naïve; n=1274), and GS-US-380-1844, GS-US-380-1878, and GS-US-380-1961 (switch; n=1610)?were included. HIV-1 genotype and subtype were determined at baseline for all naïve study participants, and for a subset in the switch studies by historical or archive genotyping. Treatment response was assessed by FDA snapshot analysis at Week 48 (HIV-1 RNA < 50 copies/mL, HIV-1 RNA ≥ 50 copies/mL, or no virologic data).
Results: In the naïve studies, HIV-1 subtype B was predominant (1138/1274 [89%] B vs. 136/1274 [11%] non-B). Efficacy of B/F/TAF at Week 48 (HIV-1 RNA < 50 copies/mL) was similar for individuals with HIV-1 subtype B or non-B (91% vs. 89%) (Table 1). Similar efficacy by subtype was seen for the comparator groups (ABC/DTG/3TC and DTG+F/TAF). There was no emergent drug resistance in any participant regardless of subtype, pre-existing resistance, or treatment group. In the switch studies, non-B subtype was well represented (639/1610 [40%] B, 384/1610 [24%] non-B, 587/1610 [36%] unknown subtype [testing not performed]). The proportion of B/F/TAF or comparator group participants with HIV-1 RNA < 50 copies/mL at Week 48 was similar for those with subtype B or non-B (94% vs. 92% for B/F/TAF). There was no emergent drug resistance in any participant treated with a BIC- or DTG-based regimen, regardless of subtype or pre-existing resistance, but 2 participants (both subtype B) had emergent NRTI resistance in other comparator arms. The proportion of subtype B vs. non-B participants with pre-existing resistance was similar, and pre-existing resistance did not contribute to virologic failure or additional resistance development.
Conclusions: HIV-1 subtype (B or non-B) had no effect on the efficacy of B/F/TAF in treatment-naïve or switch studies. No participant developed resistance to B/F/TAF regardless of HIV-1 subtype or pre-existing resistance.

HIV-1 Subtype CategoryNumber of Subjects n (%)
 B/F/TAFComparator Groups
 HIV-1 RNA < 50 copies/mLHIV-1 RNA ≥ 50 copies/mLNo dataHIV-1 RNA < 50 copies/mLHIV-1 RNA ≥ 50 copies/mLNo data
Naïve Studies (GS-US-380-1489, GS-US-380-1490)All Subjects576/634 (90.9%)17/634 (2.7%)41/634 (6.5%)595/640 (93.0%)12/640 (1.9%)33/640 (5.2%)
 B513/563 (91.1%)16/563 (2.8%)34/563 (6.0%)535/575 (93.0%)11/575 (1.9%)29/575 (5.0%)
 Non-B63/71 (88.7%)1/71 (1.4%)7/71 (9.9%)60/65 (92.3%)1/65 (1.5%)4/65 (6.2%)
Switch Studies (GS-US-380-1844, GS-US-380-1878, GS-US-380-1961)All Subjects755/806 (93.7%)12/806 (1.5%)39/806 (4.8%)747/804 (92.9%)10/804 (1.2%)47/804 (5.8%)
 B374/396 (94.4%)7/396 (1.8%)15/396 (3.8%)223/243 (91.8%)6/243 (2.5%)14/243 (5.8%)
 Non-B177/192 (92.2%)4/192 (2.1%)11/192 (5.7%)183/192 (95.3%)2/192 (1.0%)7/192 (3.6%)
 Unknown204/218 (93.6%)1/218 (0.5%)13/218 (6.0%)341/369 (92.4%)2/369 (0.5%)26/369 (7.0%)
[Table 1]