Week 96 Results of a Phase 3 Double-Blind Study Comparing Doravirine/Islatravir (DOR/ISL) to Biktarvy (B/F/TAF) in Virologically Suppressed HIV-1 Adults

Original article title: "", Author: Roger Paredes

In a double-blind study,MSD New DrugDoravirine (DOR)/Islatravir (ISL) (100/0.75 mg) was non-inferior to continued Bictegravir in maintaining viral suppression at Week 48, but the side effects of Doravirine/Islatravir were more pronounced.We report the results of Week 96 here.

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Adults without prior treatment failure and HIV-1 RNA <50 copies/mL were randomized (1:1) to switch to DOR/ISL or continue B/F/TAF after ≥3 months on the existing regimen of B/F/TAF. The protocol specified that treatment should be discontinued if there was a decline in CD4+ T-cell and/or total lymphocyte (TL) count (e.g., a decrease of ≥30%). Efficacy was assessed using the FDA snapshot algorithm, including the full analysis set (FAS, all patients who received ≥1 dose of study drug) and the modified FAS (mFAS, excluding patients who discontinued due to cell count decline before Week 96).

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A total of 641 patients participated in this drug research trial (322 in the doravirine/islatravir [DOR/ISL] group and 319 in the bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF] group). At Week 96, the results for HIV-1 RNA <50 copies/mL were as follows: In the Full Analysis Set (FAS), DOR/ISL was 84.8% compared to 90.9% for B/F/TAF (difference -6.1%, 95% CI -11.3, -1.1); in the modified FAS (mFAS, excluding 13 DOR/ISL participants with reduced cell counts), it was 88.3% versus 90.9% (difference -2.6%, 95% CI -7.5, 2.2). Two participants in the DOR/ISL group and one participant in the B/F/TAF group had HIV-1 RNA ≥50 copies/mL. Two participants in the DOR/ISL group experienced virologic failure (VF, defined as two consecutive measurements of HIV-1 RNA ≥200 copies/mL), with undetectable ISL plasma concentrations at the time of VF. The mean CD4+ T-cell and TL counts were lower in the DOR/ISL group than in the B/F/TAF group. The overall incidence of adverse events, including infections, was comparable between the groups. More patients in the DOR/ISL group experienced treatment-related adverse events leading to discontinuation, primarily due to decreases in CD4+ T-cell and TL counts (details are provided in the table).

Participants who switched from B/F/TAF (Biktarvy) to DOR/ISL (Doravirine/Islatravir) (100/0.75mg) maintained viral suppression through Week 96.The discontinuation criteria specified in the protocol for CD4+ T-cell and/or TL count reduction led to intergroup efficacy differences in the FAS. The reduction in cell count resulted in numerous...Treatment-related adverse events (AE) and discontinuation due to DOR/ISL.