Background: Studies 1844 and 1878 demonstrated the non-inferior efficacy of switching suppressed HIV-1-infected adults to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing dolutegravir (DTG)- or boosted protease inhibitor (bPI)-containing triple therapy. After week 48, remaining participants in the DTG and bPI groups switched to B/F/TAF in an open-label extension (OLE) phase. Here, resistance analyses and virologic outcomes for these participants are described.
Methods: Participants included in this analysis were randomized at baseline to continue their DTG- or bPI-based regimen, completed 48 weeks, and switched to B/F/TAF in the OLE. Preexisting HIV-1 drug resistance was assessed by historical genotypes (documented resistance to study drugs was excluded) and retrospective baseline proviral DNA genotyping (participants with resistance to study drugs detected post-OLE switch were allowed to remain on study). Virologic outcomes were based on last available HIV-1 RNA during B/F/TAF treatment.
Results: Altogether, 510 participants switched to B/F/TAF in the OLE and were treated for a median of 60 weeks (IQR 48-72 weeks). Cumulative baseline reverse transcriptase genotypic data were available for 73% (373/510); integrase data were available for 49% (248/510). Primary NRTI resistance (-R) and INSTI-R substitutions preexisted in 11% (41/373) and 3.6% (9/248), respectively (Table 1). DNA genotyping detected previously undocumented M184V/I in 5.4% (20/373), and thymidine analog mutations (TAMs) were observed in 8.0% (30/373). Through the time of analysis, 99% (503/510) of participants had HIV-1 RNA < 50 copies/mL at last visit, including 95% (19/20) with archived M184V/I, 100% (30/30) with TAMs, and 100% (9/9) with INSTI-R. During the OLE 5 participants met criteria for resistance testing with no treatment-emergent resistance.
Conclusions: Among participants who switched to B/F/TAF in the OLE of studies 1844 and 1878, high rates of virologic suppression were maintained for >1 year of B/F/TAF treatment with no resistance development despite significant underlying preexisting resistance substitutions, such as M184V/I and TAMs. These findings indicate that B/F/TAF may have utility as a switch option in a broad range of patients, including those with certain preexisting resistance.

Drug ResistanceBy Historical GenotypeBy Proviral GenotypeCumulative GenotypeHIV-1 RNA <50 copies/mL at Last Visit
Primary NRTI3.3% (9/269)15% (36/237)11% (41/373)98% (40/41)
M184V/I08.4% (20/237)5.4% (20/373)95% (19/20)
TAMs3.3% (9/269)11% (25/237)8.0% (30/373)100% (30/30)
Primary INSTI7.7% (1/13)3.4% (8/237)3.6% (9/248)100% (9/9)
[Table 1. Baseline Resistance and B/F/TAF Efficacy in OLE Phase of Studies 1844 and 1878, % (n/N)]

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