Patients with HIV who were virally suppressed when using the combination therapy of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) (Biktarvy; Gilead Sciences) or oral antiretroviral therapy (ART) had noninferior results when switching to the single-tablet, daily dose of doravirine/islatravir (100/0.25 mg) (Merck), according to abstracts presented during the late-breaking antiviral therapy session held on the last day of the Conference on Retroviruses and Opportunistic Infections 2025, held in San Francisco, California, from March 9 to March 12. The 2 abstracts were presented among a full hour of breaking research.
Doravirine/Islatravir Maintained Viral Suppression in Patients Switching Medication
Amy Colson, MD, MPH, research director at the Community Resource Initiative in Boston, Massachusetts, presented the first of the abstracts focused on doravirine/islatravir.
“Prior phase 3 studies of doravirine and islatravir, using a daily islatravir dose of 0.75 mg, showed declines in the CD4 count and the absolute lymphocyte count,” said Colson. “A phase 2b dose-finding study…suggests that such declines would not be expected with the lower 0.25-mg daily islatravir dose used in this study.”
The first of the studies aimed to evaluate whether a combination therapy of doravirine/islatravir at 100 mg/0.25 mg dose shares similar efficacy to BIC/FTC/TAF in patients who were virally suppressed when using BIC/FTC/TAF. The results come from an ongoing phase 3 trial.
Participants of the study were all adults with HIV-1 who had no history of treatment failure or resistance to doravirine and were virally suppressed with BIC/FTC/TAF for 3 or more months. The primary end point for the 48-week trial was the percentage of participants who had an HIV-1 RNA of 50 or more copies/mL. A confirmed decline in total lymphocytes or CD4 T-cell count required discontinuation.
There were 513 participants who were randomized 2:1 to doravirine/islatravir or continued using BIC/FTC/TAF, with 342 and 171 participants in each group, respectively. The mean (SD) age of the cohort was 47.6 (12.9) years. Participants assigned female at birth made up 21.4% of the group, and 60.8% of the individuals were White.
The late-breaking antiviral session was highlighted by new results on DOR/ISL compared with BIC/FTC/TAF | Image credit: gamjai – stock.adobe.com
A total of 5 participants in the doravirine/islatravir group and 1 in the BIC/FTC/TAF group had an HIV-1 RNA of 50 or more copies/mL after 48 weeks, with 91.5% of the participants in the doravirine/islatravir group and 94.2% of the participants in the BIC/FTC/TAF group reporting HIV-1 RNA of less than 50 copies/mL, proving doravirine/islatravir to be noninferior. Discontinuation due to a lack of efficacy was reported in 1 participant using doravirine/islatravir. Adverse events due to the drug were similar between the doravirine/islatravir and the BIC/FTC/TAF groups (10.2% and 9.4%, respectively), and discontinuations due to those adverse events were also similar (2.9% and 1.8%). Mean change in CD4 T-cell count and total lymphocyte count were not different between the groups after 48 weeks.
“In adults with virologic suppression, switching to the once-daily fixed dose combination of doravirine 100 mg and islatravir 0.25 mg is noninferior to continuing [BIC/FTC/TAF],” said Colson. “Importantly, islatravir dosed at a daily dose of 0.25 mg did not adversely affect the lymphocyte count or the CD4 count.”
The researchers concluded that these results proved that doravirine/islatravir was noninferior to BIC/FTC/TAF when it came to maintaining viral suppression. Other trials delved into the efficacy of doravirine/islatravir compared with other oral ART.
Doravirine/Islatravir as Effective as Other Oral ART
Chloe Orkin, MBBCH, MSc, professor of infection and inequities at Queen Mary University of London, presented trial results assessing the efficacy of doravirine/islatravir when switching from oral ART with CD4 and total lymphocyte counts acting as secondary end points.2
Participants of this study were all adults with HIV-1 RNA of less than 50 copies/mL when using any oral ART that required 2 or 3 drugs. Participants could not have a history of treatment failure or have resistance to doravirine that they were aware of. The percentage of participants who had 50 or more copies/mL of HIV-1 RNA after 48 weeks was the primary efficacy end point. Confirmed total lymphocytes and CD4 count came after discontinuation.
All 551 participants were randomized 2:1 to either doravirine/islatravir or were told to continue their oral ART regimen, totaling 366 in the doravirine/islatravir group and 185 in the ART group. The mean age of the group was 49.8 (12.3) years, and 39.7% were female at birth. A total of 45.4% of the participants were Black. The median (IQR) duration of ART was 3.8 (2.0-6.3) years, and the median time since diagnosis was 13.3 (7.2-20.4) years.
Only 5 participants (1.4%) reported an HIV-1 RNA of 50 or more copies/mL after 48 weeks on doravirine/islatravir compared with 9 (4.9%) on ART. A total of 95.6% of the participants on doravirine/islatravir and 91.9% of the participants on ART reported HIV-1 RNA of less than 50 copies/mL after 48 weeks, proving that doravirine/islatravir was not inferior to other forms of ART. However, participants on doravirine/islatravir reported more adverse events compared with those in the ART group (12.0% vs 4.9%), with only 1 leading to discontinuation. The 2 groups had similar mean changes of CD4 T-cell and total lymphocyte counts after 48 weeks.
“Concerning weight gain, there was more weight gain on doravirine/islatravir,” said Orkin. “However, this was driven by the removal of weight suppressive ART.”
Both of these studies showed that doravirine/islatravir was not significantly inferior to either BIC/FTC/TAF or oral ART, providing a daily, single-tablet alternative to those who require ART. These results offer the potential to reduce the number of medications that people living with HIV need to consume daily, making adherence easier to encourage.
“Doravirine/islatravir may provide an efficacious, non–entity–based switch option for people living with HIV,” Orkin concluded.
Other Late-Breaking Studies Focused on Antiviral Therapies
The late-breaking antiviral therapy session also featured new data on long-acting methods of treating patients with virally suppressed HIV. Specifically, both new abstracts focused on the efficacy of long-acting cabotegravir in combination with other treatments. The randomized CARES trial tested the efficacy of cabotegravir in combination with rilpivirine in patients living in Africa who received the treatment for 96 weeks. The researchers found that 96 weeks of long-acting cabotegravir/rilpivirine in these patients had noninferior results when compared with oral ART.3
The last session saw the results of the EMBRACE study presented,4 which focused on long-acting cabotegravir combined with VH3810109 (N6LS), a CD4 binding site antibody that can be administered intravenously or subcutaneously.
“N6LS is unique because it has the greatest breadth for coverage of HIV-1,” said Babafemi Taiwo, MD, MBBS, chief of the Division of Infectious Diseases at Northwestern University and coauthor of the study.
The researchers found that N6LS combined with recombinant human hyaluronidase PH20 administered every 4 months along with a monthly dose of cabotegravir was able to maintain viral suppression in all patients who were sensitive to N6LS.
These results promise new frontiers in HIV research, offering patients a plethora of new options to maintain viral suppression and live their lives without fear of spreading HIV. Continued research into methods of viral suppression can allow for any needed change in regimen and potential toxicity to become only short-term obstacles rather than long-term ones.
“Based on these results, we have selected N6LS [intravenous], which showed 96% suppression, for further evaluation in part 2 of the EMBRACE study, where it will be studied every 6 months and in combination with [long-acting cabotegravir],” Taiwo concluded.
References
- Fox M, Mills AM, Ramgopal M, et al. Switch to DOR/ISL (100/0.25 mg) QD from BIC/FTC/TAF: a blinded phase III study in adults with HIV-1. Presented at: Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 204A.
- Fox M, Mngqibisa R, Velez JD, et al. Switch to DOR/ISL (100/0.25 mg) QD from oral ART: an open-label phase III study in adults with HIV-1. Presented at: Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 204B
- Kityo C, Mambule IK, Sokhela SM, et al. Randomized trial of long-acting cabotegravir and rilpivirine in Africa (CARES): week 96 results. Presented at: Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 202.
- Leone P, Taiwo B, Gartland M, et al. VH3810109 (N6LS) efficacy and safety in adults who are virologically suppressed: the EMBRACE study. Presented at: Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 203.
