514 – Switch to DOR/ISL (100/0.25 mg) QD From BIC/FTC/TAF: 96-Week Update From a Blinded Phase III Study

Background

The NNRTI doravirine (DOR) and the investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) islatravir (ISL) have complementary mechanisms of action and resistance profiles. The primary analysis of the MK8591A-052 study in people living with HIV-1 demonstrated that switching to DOR/ISL 100 mg/0.25 mg was noninferior to continuing bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in maintaining virologic suppression at Week 48. Here we present Week 96 efficacy and safety data from this study.

Methods

Phase 3, double-blind clinical trial (NCT05630755) in adults with HIV-1 RNA <50 copies/mL for ≥3 months on BIC/FTC/TAF, CD4+ T-cell count ≥50 cells/mm³, and no prior therapy failure or known DOR resistance. Participants were randomized 2:1 to switch to DOR/ISL (100/0.25 mg) or continue BIC/FTC/TAF. Discontinuation was required for confirmed decline in total lymphocytes (≥30% and <1.0 x10⁹/L) or CD4+ T-cells (≥30% and either <350 cells/mm³ if ≥350 at baseline or <200 cells/mm³ if ≤349 at baseline). The proportion of participants with HIV-1 RNA ≥50 copies/mL (FDA snapshot) at Week 96 was a secondary endpoint. Other virologic outcomes (HIV-1 RNA <50 and <200 copies/mL), safety, and tolerability through Week 96 were also assessed.

Results

Overall, 342 participants were switched to DOR/ISL and 171 continued BIC/FTC/TAF. At Week 96 (Table), 5 (1.5%) participants on DOR/ISL vs 2 (1.2%) on BIC/FTC/TAF had confirmed HIV-1 RNA ≥50 copies/mL (difference: 0.3%, 95% confidence interval: -2.8, 2.4); 2 (0.6%) vs 0, respectively, had discontinued due to lack of efficacy; and 3 (0.9%) vs 1 (0.6%), respectively, had discontinued for other reasons with HIV-1 RNA ≥50 copies/mL at discontinuation. Proportions of participants with adverse events (AEs) through Week 96 were similar between groups (Table). The Week 96 DOR/ISL AE profile was similar to Week 48 with no new safety findings. There were no differences between arms in CD4+ T-cell or total lymphocyte count (TLC) changes through Week 96 (Table). In both groups, 0.6% (DOR/ISL n=2, BIC/FTC/TAF n=1) discontinued due to protocol-specified decreases in CD4+ T-cell and/or TLC counts.

Conclusions

DOR/ISL (100/0.25 mg) maintained a high rate of virologic suppression and had similar efficacy to BIC/FTC/TAF at Week 96. DOR/ISL demonstrated an AE profile comparable to BIC/FTC/TAF and did not adversely affect lymphocytes. These findings are consistent with the study’s primary Week 48 results.

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