Late-breaking phase 3 data presented at CROI 2026 highlight the continued promise of the two-drug regimen doravirine/islatravir (DOR/ISL) across multiple treatment settings, including in previously untreated adults and in those switching from established antiretroviral regimens.
The findings span three trials—MK-8591A-053 in treatment-naive adults and MK-8591A-052 and MK-8591A-051 in virologically suppressed individuals who switched therapy from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; Biktarvy, Gilead) or other approved regimens—offering a broad look at the regimen’s performance through weeks 48 and 96 (oral abstract 177; poster abstracts 514 and 515).
“DOR/ISL demonstrated noninferior efficacy and a similar safety profile to BIC/FTC/TAF at week 48 in people living with HIV-1 who had not previously received treatment, including those with advanced disease,” said Jürgen Rockstroh, MD, a professor of medicine and the head of the HIV Outpatient Clinic at the University of Bonn, in Germany. “In addition, DOR/ISL had a similar safety profile to BIC/FTC/TAF.
“The 48-week findings strengthen the evidence for DOR/ISL’s potential as a new HIV treatment option to help meet the evolving needs of people living with HIV,” Dr. Rockstroh added.
Durable Suppression After Switching From BIC/FTC/TAF
In MK-8591A-052 (abstract 514), a double-blind phase 3 study evaluating adults who were virologically suppressed on BIC/FTC/TAF, switching to once-daily DOR/ISL (100/0.25 mg) maintained high rates of viral suppression through 96 weeks.
At week 96, confirmed HIV-1 RNA at or above 50 copies/mL occurred in 1.5% of participants in the DOR/ISL arm versus 1.2% in those continuing BIC/FTC/TAF. Virologic suppression (<50 copies/mL) was maintained in 88.9% of the DOR/ISL group and 90.1% of the BIC/FTC/TAF group. CD4+ T-cell and total lymphocyte counts remained stable and comparable between groups through week 96.
Treatment-emergent resistance was rare. Through week 96, no resistance was detected in the BIC/FTC/TAF arm, and one case was observed in the DOR/ISL group (0.3%) in a post-hoc analysis. Safety outcomes were similarly reassuring. Adverse event rates were comparable between groups, with no deaths and low rates of discontinuation due to adverse events.
Metabolic parameters—including LDL cholesterol, non-HDL cholesterol, insulin resistance, and weight—showed no clinically meaningful differences between arms.
Switch Study Confirms Findings Across Baseline Regimens
Findings were also reported from MK-8591A-051, an open-label phase 3 trial evaluating switching to DOR/ISL from a variety of two- or three-drug oral regimens (abstract 515).
Among participants who switched to DOR/ISL at baseline (group 1), 92.6% maintained HIV-1 RNA below 50 copies/mL at week 96. In those who switched at week 48 (group 2), suppression rates at week 96 (after 48 weeks on DOR/ISL) were 96.6%, comparable to group 1 at week 48.
No treatment-emergent resistance to DOR or ISL was observed through week 96, the investigators reported.
Total lymphocyte and CD4+ T-cell counts remained stable across groups. Adverse event rates during the first 48 weeks of DOR/ISL were similar whether participants switched at baseline or later. Weight changes were generally modest, with greater gains observed primarily in participants switching from weight-suppressive regimens containing efavirenz or tenofovir disoproxil fumarate.
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A Potential New Two-Drug Option
Taken together, the three studies demonstrate that DOR/ISL achieves noninferior efficacy compared with established three-drug regimens in treatment-naive individuals and maintains durable suppression through 96 weeks in virologically suppressed adults who switch therapy.
Remaining questions center on longer-term durability.
“MK-8591A-053 will continue to assess the efficacy and safety of DOR/ISL through week 144. Detailed findings from these studies are expected to be presented at future scientific congresses,” Dr. Rockstroh said.
The research was funded by Merck.