633 - Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Efficacy in Participants with Pre-Existing Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials

Background: Pre-existing drug resistance can affect the efficacy of antiretroviral therapy. Studies in treatment-naïve and virologically suppressed participants have demonstrated safety and efficacy of B/F/TAF, including in patients with M184V/I mutations. In this pooled analysis, we investigated virologic outcomes after 48 weeks of B/F/TAF treatment in individuals with pre-existing integrase strand transfer inhibitor resistance (INSTI-R).

Methods: Although INSTI-R was prohibited per study entry criteria, pre-existing INSTI-R (T66A/I/K, E92G/Q, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, R263K) was evaluated in participants from studies 1489, 1490, 1844, 1878, 4030. INSTI-R was assessed by historical genotypes and/or retrospective deepType HIV assay (Seq-IT, Germany), GenoSure IN, GenoSure Archive (Monogram Biosciences). Virologic outcomes were defined by last on-treatment observation carried forward (LOCF) method.

Results: Pre-existing primary INSTI-R substitutions were detected in 20/1907 participants (1.0%) after enrolment.  Of the 20, 75% were male, 30% white, and 85% had HIV-1 subtype B, baseline median CD4 counts of 594 (IQR 517, 700), and median age of 52 (43, 59) years. One participant was treatment-naïve with a baseline viral load of 30,000 copies/ml and had Q148H (+ G140S on plasma RNA genotype) and was sensitive to bictegravir (< 2.5-fold change). The other 19 participants were virologically suppressed and had E92G (n=3), Y143C (n=2), Y143H (n=4), S147G (n=2), N155S (n=1), Q148H (n=3), Q148K (n=1), Q148R (n=1), or R263K (n=2) INSTI-R mutations by DNA genotype. The treatment-naïve individual was suppressed by Week 4 and maintained viral loads of < 50 copies/mL through Week 48. All suppressed participants had HIV RNA < 50 copies/mL throughout Week 48.  All study participants had virologic success by LOCF (< 50 copies/mL) at Week 48.

Conclusion: Participants with primary INSTI-R substitutions had or maintained virologic suppression through 48 weeks of B/F/TAF treatment. Consistent with the potent in vitro activity of bictegravir against many INSTI-R mutations, these virologic outcomes suggest that B/F/TAF may have potential as a treatment option for some patients with pre-existing INSTI-R, if confirmed by further studies.