Background
In the ALLIANCE study (GS-US-380-4458; NCT03547908), bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was noninferior to dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+F/TDF) at achieving HIV-1 RNA suppression at Week (W) 48 in treatment-naïve adults with HIV-1/hepatitis B virus (HBV) coinfection, with high rates of suppression maintained through End of Study (EoS). We present HIV-1 resistance analyses through EoS for the B/F/TAF group (through the ≥96W randomized phase and 48W of open-label extension [OLE]) and the DTG+F/TDF to B/F/TAF group (switched from DTG+F/TDF to B/F/TAF at OLE start); additionally, we report data for the DTG+F/TDF group through the randomized phase.
Methods
Population sequencing of HIV-1 protease (PR) and reverse transcriptase (RT) was performed at screening. Historical PR, RT, and integrase (IN) genotypes were also collected, if available. Participants with virologic failure (VF; rebound in HIV-1 RNA ≥50 copies (c)/mL after achieving <50 c/mL or >1 log10 increase from nadir, subsequently confirmed and ≥200 c/mL; or HIV-1 RNA ≥200 c/mL at last visit) underwent genotypic/phenotypic resistance analyses for PR/RT/IN. Participants who did not resuppress (<50 c/mL) were included in the final resistance analysis population (RAP).
Results
Preexisting primary resistance-associated mutations (RAMs) were detected in PR (1-3%) and RT (2-10%) across treatment groups, including M184I (n=1), M41L (n=2), and K219N (n=1) in RT, and did not affect virologic suppression through EoS. The final RAP consisted of 14 participants: DTG+F/TDF group, 7/122 (6%); B/F/TAF group, 6/119 (5%); and DTG+F/TDF to B/F/TAF group, 1/89 (1%). No participants developed primary RAMs, including 6 who had multiple (2-4) confirmed VFs. Another 8 participants who did not qualify for the final RAP had resistance testing during the study. Of these, 1 from the DTG+F/TDF group with reported nonadherence developed K70E in RT at W24 (conferring low-level resistance to TDF) and M184V/I in RT at W36 (conferring resistance to emtricitabine); no others developed resistance to study drugs.
Conclusions
Treatment outcomes were not affected by the presence of preexisting nucleos(t)ide reverse transcriptase inhibitor (NRTI) RAMs, and no participant in the final RAP developed resistance to study drugs. One participant in the DTG+F/TDF group with reported nonadherence developed primary NRTI RAMs. Through EoS, B/F/TAF or DTG+F/TDF maintained high rates of HIV-1 virologic suppression.
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