Background: Study 4030 is a phase 3, randomized, double-blinded study (n=565) of HIV-1 RNA suppressed participants switching to B/F/TAF or dolutegravir (DTG)+F/TAF from DTG+F/tenofovir disoproxil fumarate (TDF) or DTG+F/TAF. NRTI, NNRTI, and PI resistance (-R) was allowed, but INSTI-R was excluded. We present FDA Snapshot outcomes at Week 48 by pre-existing resistance.
Methods: Historical plasma HIV-1 RNA genotypes and baseline proviral DNA genotypes (GenoSure Archive) were analyzed. Documented or suspected NRTI-R was grouped for stratification: 1) K65R/E/N or ≥3 TAMs including M41L or L210W (TAMs: D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R) (±M184V/I), 2) M184V/I (if not in group 1), any other set of TAMs, K70E/G/M/Q/S/T, L74I/V, V75A/S/M/T, Y115F, T69D, or Q151M, or 3) no major NRTI-R mutations, and no suspected resistance. Resistance analyses were performed on samples with HIV-1 RNA ≥200 copies/mL at confirmed virologic failure, discontinuation, or Week 48, if participants did not resuppress HIV-1 RNA to < 50 copies/mL on study drug.
Results: Historical genotypes were available from 285/565 participants. Retrospective analysis of archived mutations by HIV proviral DNA genotype were determined for 391/565 participants. In total, 83% (470/565) of participants had baseline genotypic data available with major NRTI-R detected in 24% (138/565), including 5% (30/565) with K65R/E/N or ≥3 TAMs and 19% (108/565) with other NRTI-R mutations. M184V/I was present in 14% (81/565). Preexisting major INSTI-R mutations were found in 4% (20/565) of participants. Primary NNRTI- and PI-R mutations were present in 21% (118/565) and 7% (38/565) of participants. High rates of viral suppression were maintained in all groups through Week 48 (Table 1). Three participants met criteria for resistance analysis (all in DTG+F/TAF arm); none developed treatment-emergent resistance to study drugs.
Conclusions: Participants with NRTI resistance, much of which was previously undocumented, maintained suppression 48 weeks after switching to B/F/TAF or DTG+F/TAF triple therapy. There were low rates of virologic failure using either drug regimen, with no treatment emergent resistance.

 B/F/TAF (n=284)DTG+F/TAF (n=281)
NRTI Resistance CategoryResistance Classification at RandomizationFinal Resistance Classification (including proviral DNA genotype)Resistance Classification at RandomizationFinal Resistance Classification (including proviral DNA genotype)
All Participants93% (265/284)91% (256/281)
Group 1: K65R or ≥3 TAMs86% (6/7)a 94% (15/16)a100% (8/8)a100% (14/14)a
Group 2: Other NRTI-R94% (30/32)a93% (51/55)a97% (30/31)a96% (51/53)a
M184V/I (Groups 1 or 2)N/A89% (42/47)bN/A94% (32/34)b
Group 3: No NRTI-R or no R data93% (229/245)93% (199/213)90% (218/242)89% (191/214)
a. All participants had HIV-1 RNA < 50 copies/mL at Week 48 or their last visit. b. M184V/I was seen by historical genotype in 22 and 18 participants in the B/F/TAF and DTG+F/TAF groups, respectively. Previously undocumented M184V/I was uncovered after randomization by proviral DNA genotyping in 25 and 16 participants in the B/F/TAF and DTG+F/TAF groups, respectively.
[Table 1. HIV-1 RNA < 50 copies/mL at Week 48, by NRTI resistance category]

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