MOPEB241

Title

Keeping the pressure on archived NRTI resistance: Switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) triple therapy in study 4030

Presenter

Rima Acosta

Authors

R. Acosta, M. Willkom, K. Andreatta, H. Liu, R. Martin, S. Chang, A. Parvangada, H. Martin, S. Collins, K. White

Institutions

Gilead Sciences, Foster City, United States

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 Category	Resistance Classification at Randomization	Final Resistance Classification (including proviral DNA genotype)	Resistance Classification at Randomization	Final Resistance Classification (including proviral DNA genotype)
All Participants	93% (265/284)		91% (256/281)
Group 1: K65R or ≥3 TAMs	86% (6/7)^a	94% (15/16)^a	100% (8/8)^a	100% (14/14)^a
Group 2: Other NRTI-R	94% (30/32)^a	93% (51/55)^a	97% (30/31)^a	96% (51/53)^a
M184V/I (Groups 1 or 2)	N/A	89% (42/47)^b	N/A	94% (32/34)^b
Group 3: No NRTI-R or no R data	93% (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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