Bictegravir (B) is coformulated with the nucleoside/tide reverse transcriptase inhibitors (NRTIs) emtricitabine (F) and tenofovir alafenamide fumarate (TAF) (B/F/TAF). Study 4030 is an ongoing, fully enrolled, phase 3, randomized, double-blinded study (n=565) of HIV-1 RNA suppressed participants on QD dolutegravir (DTG) + F/TAF or F/tenofovir disoproxil fumarate (TDF) switching 1:1 to DTG + F/TAF or B/F/TAF for 48 weeks. Documented INSTI resistance was not enrolled if known at randomization, but all NRTI, NNRTI, and PI resistance was allowed.
Proviral DNA genotypes (GenoSure Archive) from baseline samples and historical plasma HIV-1 RNA genotypes were analyzed. Documented or suspected NRTI resistance was assigned to group 1) K65R/E/N or ≥3 TAMs containing M41L or L210W (TAMs: D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), group 2) M184I/V, any other set of TAMs, K70E/G/M/Q/S/T, L74I/V, V75A/S/M/T, Y115F, T69D, or Q151M, or group 3) no major NRTI resistance. Virologic outcomes used last available on-treatment HIV-1 RNA with the blinded Week 12 IDMC data cut.
Historical genotypes were available from 285/565 participants (50%). Retrospective analysis of archived mutations by HIV DNA genotype were determined for 377/565 participants; 200 also had historical genotypes. In total, 82% (462/565) of participants had pre-switch genotypic data available resulting in 24% with major NRTI resistance: 5% (29/565) in group 1 (K65R or ≥3TAMs) and 18% (104/565) in group 2 (other NRTI mutations). M184V/I was present in 17% (77/462) of participants with data. HIV DNA genotyping identified previously unknown major NRTI resistance in 15% of participants (58/377). Pre-existing INSTI mutations were found in 5% of participants (19/399): T97A (n=12), N155S (N=1), Y143H (n=2), R263K (n=2), Q148H+G140S (n=1), and S147G (n=1). Primary non-nucleoside RT inhibitor and protease inhibitor resistance mutations were present in 24% (113/462) and 8% (36/462) of participants. At this interim analysis, HIV-1 RNA <50 copies/mL was maintained in 99% of participants, 97% (28/29) in group 1, 99% (103/104) in group 2, 97% (75/77) with M184V/I, and 100% (19/19) with INSTI-R.
This study found frequent NRTI resistance in suppressed participants switching from a DTG + F/TDF or F/TAF regimen, much of which was previously undocumented. Early data show high suppression using potent triple therapy of B/F/TAF or DTG + F/TAF.