Abstract Body


Doravirine (DOR), an approved NNRTI, and Islatravir (ISL), an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI), have complementary mechanisms of action and resistance profiles. We report week 48 results from a phase 3, open-label, non-inferiority trial (P017, NCT04223778) evaluating a switch from oral combination ART to DOR/ISL (100/0.75mg), a once-daily single-tablet regimen.


Virologically suppressed adults on any stable oral 2- or 3-drug ART for ≥3 months with no history of treatment failure or virologic resistance to DOR were randomized (1:1) to switch to DOR/ISL or continue baseline ART (bART), stratified by bART regimen (PI-based, InSTI-based, Other). The primary endpoint was % of participants (pts) with HIV-1 RNA ≥50 c/mL at week 48 (FDA Snapshot; non-inferiority margin 4%). Resistance was assessed in pts with clinically significant confirmed viremia (CSCV; 2 consecutive measures of HIV-1 RNA ≥200 c/mL).


672 pts were randomized and treated with open-label DOR/ISL (n=336) or bART (n=336); 37% were female, 27% Black, mean age 45.5 (±11.7) years. bART was PI-based in 14%, InSTI-based in 52%, and Other (mainly NNRTI-based) in 34%; mean duration before study 39.4 months. At week 48, 0% on DOR/ISL and 1.5% on bART had HIV-1 RNA ≥50 c/mL (difference -1.5; 95%CI -3.4, -0.3), while 95.2% and 94.3% respectively had HIV-1 RNA < 50 c/mL (Table). CSCV occurred in 3 pts (1%) on bART (1 InSTI-based; 2 NNRTI-based), all had resistance to ≥1 component of their regimen. Mean change from baseline in CD4+ T-cell count at week 48 was -30.3 and +38.8 cells/mm3 for DOR/ISL and bART, respectively (difference ‑66.7, 95%CI -95.8, -37.7). Total lymphocyte count was also significantly reduced in the DOR/ISL group (Table). Rates of drug-related adverse events (AEs) (19.6%, 8.9%) and discontinuation due to AEs (2.1%, 0.3%) were higher in the DOR/ISL group. Rates of Grade 3-4 AEs (6.8%, 7.4%) and serious AEs (4.2%, 3.9%) were similar between groups. One death occurred (in bART group) due to motor vehicle accident. Infection rates were comparable between treatment groups (33.6% each) and no CDC AIDS-defining Category C events occurred.


Switching to DOR/ISL (100/0.75mg) was non-inferior to continuing bART for maintaining viral suppression at week 48 and was generally well tolerated. No virologic failure was observed with DOR/ISL. Decreases in CD4+ T-cells and total lymphocytes with DOR/ISL were not associated with differences in infection-related AEs.

Table. Selected Efficacy & Safety Outcomes, DOR/ISL (100/0.75mg) P017