Investigational combo noninferior to current HIV therapy
Key takeaways:
- A combination of doravirine (DOR) and islatravir (ISL) was noninferior to current suppressive therapies among adults with HIV.
- No treatment-emergent resistance to DOR or ISL was detected.
SAN FRANCISCO — Data from two studies suggest that a once-daily combination therapy of doravirine and islatravir was noninferior to current, baseline suppressive therapies among adults with HIV.
“There remains a need for novel antiretroviral regimens that have high potency and low risk of long-term toxicity,” Amy Colson, MD, MPH, research director at Community Resource Initiative, told Healio.
“Doravirine (DOR) is an approved non-nucleoside reverse transcriptase inhibitor, and islatravir (ISL) is an investigational nucleoside reverse transcriptase translocation inhibitor. Doravirine and islatravir have complementary resistance profiles which results in a high genetic barrier to resistance when the two drugs are combined,” she said.
Colson explained that previous phase 3 trials assessing DOR and ISL as a combination using a higher daily islatravir dose (0.75 mg) showed declines in the total lymphocyte and CD4 counts, whereas a phase 2b trial supported the efficacy of a lower daily islatravir dose (0.25 mg).
Colson and colleagues aimed to further investigate the efficacy and safety of the DOR/ISL combination with the lower ISL dose as a potential new daily HIV treatment option. To do so, they conducted two studies: MK-8591A-051 and MK-8591A-052, which were both presented at the Conference on Retroviruses and Opportunistic Infections.
MK-8591A-052 is an ongoing phase 3 study evaluating the efficacy and safety of switching from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) to DOR/ISL as a once-daily single-tablet regimen.
The researchers randomly assigned 513 adults with HIV who were virologically suppressed for at least 3 months and on BIC/FTC/TAF with no history of treatment failure or known resistance to DOR were 2:1 to switch to DOR/ISL or continue BIC/FTC/TAF. Among participants, mean age was 47.6, 21.4% were female at birth, 60.8% were white, 30.8% were Black and 22.8% were Latin.
MK-8591A-051 is also an ongoing phase 3 study evaluating the efficacy and safety of switching from oral ART to DOR/ISL as a once-daily single-tablet regimen.
The researchers randomly assigned 551 adults with HIV on oral two- or three-drug ART and no history of treatment failure or known virologic resistance to DOR were 2:1 to switch to DOR/ISL or continue baseline ART. Among the participants, mean age was 49.8, 39.7% were female at birth, 45.4% were Black and 14.5% were Latin.
In both trials, the researchers found that DOR/ISL was noninferior to continuing current therapies, including BIC/FTC/TAF.
Specifically, data from MK-8591A-052 showed that 1.5% on DOR/ISL had a viral load measurement of 50 copies/mL or greater at week 48 compared with 0.6% who continued BIC/FTC/TAF, whereas results from MK-8591A-051 showed that 1.4% of patients on DOR/ISL had a viral load measurement 50 copies/mL or greater at week 48 compared with 4.9% who continued baseline therapy.
Colson added that no treatment-emergent resistance to DOR or ISL was detected in either trial.
“These two large, global pivotal trials of the two-drug combination of DOR and ISL achieved positive efficacy and safety results at the primary endpoint in a virologically suppressed population of people living with HIV,” Colson said. “The trials support ongoing development of islatravir as a component of long-acting two-drug regimens.”
References:
- Fox M, et al. Abstract 204A. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.
- Fox M, et al. Abstract 204B. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.
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Fox M, et al. Abstract 204A. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.
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