Investigational HIV Treatment DOR/ISL Does Not Appear to Affect Fasting Lipids, Insulin Resistance

The investigational HIV treatment doravirine/islatravir (DOR/ISL, Merck) has been found to have no effect on fasting lipids and insulin resistance, according to new research presented at EACS 2025, in Paris.

The findings come from 48-week assessments of two phase 3 trials, where DOR/ISL was compared with both bictegravir-emtricitabine-tenofovir alafenamide (BIC/FTC/TAF; Biktarvy, Gilead) and continuing various baseline antiretroviral therapy (bART). DOR/ISL also was found to be noninferior to these treatments and have a similar safety profile.

HIV, Metabolism, and Heart Health

The data are encouraging, explained Chloe Orkin, MBBCH, MSc, the dean of healthcare transformation at Queen Mary University of London. “We are encouraged by the data presented at EACS, which show that switching to DOR/ISL from BIC/FTC/TAF had minimal impact on weight and body composition and no clinically meaningful effect on fasting lipids and the homeostatic model assessment of insulin resistance,” Dr. Orkin told Infectious Disease Special Edition.

All ART is associated with weight gain, and the condition HIV itself and ART have been linked to cardiovascular and metabolic outcomes—such as dyslipidemia and insulin resistance—in people living with HIV. “The extent of weight gain varies among different regimens,” Dr. Orkin explained. “The specific reasons for these differences are not currently known.”

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Switching Is an Option

In both phase 3 trials, adults living with HIV who had HIV RNA levels lower than 50 copies/mL and had received stable bART (ClinicalTrials.gov Identifier: NCT05631093) or BIC/FTC/TAF (NCT05630755) for at least three months were randomized 2:1 to switch to DOR/ISL or continue their current regimen. Although people with type 1 diabetes were excluded from the trials, those with type 2 were included but asked to delay their morning medications while fasting for bloodwork. In addition, study participants already receiving lipid-lowering therapy were excluded from the lipid analyses.

In the combined analysis, 708 participants switched to DOR/ISL, 185 continued bART, and 171 continued BIC/FTC/TAF. A similar number of participants started lipid-lowering therapy across the three groups (DOR/ISL, 4.8%; bART, 5.9%; BIC/FTC/TAF, 4.1%). The researchers found that mean changes from baseline in fasting lipids were minimal in those taking DOR/ISL, with no substantial differences from those taking bART or BIC/FTC/TAF. 

Similarly, the proportion of participants with type 2 diabetes who modified their medications was less than 5% across treatment groups. Again, the researchers found that mean changes in fasting insulin, glucose, and homeostatic model assessment of insulin resistance were minimal across groups.

This could be meaningful, as a growing and aging population with HIV continues to develop cardiovascular and metabolic comorbidities.

Dr. Orkin reported institutional research grants (including grants pending) from AstraZeneca, Gilead, GlaxoSmithKline, Janssen, Merck, and ViiV Healthcare; lecture fees (including service on speakers bureaus) from Bavarian Nordic, Gilead, GSK, Janssen, Merck, and ViiV Healthcare; and travel support from Bavarian Nordic, Gilead, and ViiV Healthcare.