Novel Therapies, Long-Acting Antivirals Highlight Oral Abstract Presentation

The Conference on Retroviruses and Opportunistic Infections 2026 continued to deliver breaking research on its final day, with late-breaking abstracts presented during an oral abstract session held on Wednesday. The abstract session focused on the promise of long-acting antivirals in treating HIV, with efficacy results for doravirine/islatravir (DOR/ISL) vs bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), the combination of lotivibart (N6LS) with long-acting cabotegravir (CAB LA), and bictegravir/lenacapavir (BIC/LEN) all presented before the gathered crowd.

DOR/ISL Noninferior to BIC/FTC/TAF in Phase 3 Study

Jürgen K. Rockstroh, MD, head of the HIV Outpatient Clinic at the University of Bonn in Germany, presented phase 3 data evaluating the efficacy of DOR/ISL (100/0.25 mg) compared with BIC/FTC/TAF when used as an initial therapy for HIV.¹ The data presented demonstrated efficacy through 48 weeks.

All adults included had plasma HIV-1 RNA with 500 copies/mL or more. There was no known resistance to the study intervention, no active hepatitis B in the patients, and all patients needed to be treatment-naive to be included in the study. The primary end point was to suppress viral load to less than 50 copies/mL in this population. The study took place across 20 countries, with Latin America having the highest proportion of participants (25.4%), followed by North America (21.5%) and Africa (20.9%).

“You can see that this study really resembled a truly global effort, with enrollment from 116 study sites in 20 countries,” said Rockstroh. “You see there is a large diversity involving 5 continents with pretty [similar] numbers of included individuals.”

There were 269 patients on DOR/ISL and 267 using BIC/FTC/TAF. The majority of the total population were men (75.0%), and there was a similar percentage of participants who were White (42.0%) and Black (31.9%) included in the study. Through 48 weeks, the researchers found that 91.8% and 90.6% of those respective groups were virally suppressed. Only 6 patients total discontinued treatment due to lack of efficacy: 4 in the DOR/ISL group and 2 in the BIC/FTC/TAF groups. Fifteen participants were not virally suppressed by the end of the study. The safety profiles were also similar between the 2 groups.

“[DOR/ISL] appears to be a potential non-integrase, 2-drug regimen for the initial treatment of HIV-1,” concluded Rockstroh.

Suppression Maintained After 12 Months Using N6LS With CAB LA

The results from the EMBRACE study (NCT05996471), which evaluated maintaining suppression after 12 months with N6LS taken every 4 months along with CAB LA taken once a month,² were presented by Charlotte-Paige Rolle, MD, director of research operations at Orlando Immunology Center.

The phase 2B study was conducted at 45 sites across the US and Puerto Rico. All participants needed to be between the ages of 18 and 70 years, on stable antiretroviral therapy (ART) for at least 6 months, have at least 2 measurements of less than 50 copies/mL in the year leading up to the start of the study, have no prior ART switch, and have no co-infection of hepatitis B.

“Today, we’re here to focus on that secondary end point of HIV-1 RNA greater than or equal to 50 copies/mL at month 12 per the FDA snapshot,” explained Rolle.

There were 125 participants included in this study: 50 in the intravenous (IV) N6LS with CAB LA group, 49 in the subcutaneous (SC) N6LS plus CAB LA group, and 26 in the oral standard of care group. A total of 83% of the total population comprised men and 63% were White, 43% of whom identified themselves as Hispanic or Latin American.

Rolle compared the 12-month efficacy to that of the 6-month results, which were largely similar. The researchers found that 94% of those using IV N6LS with CAB LA were virally suppressed compared with 88% using oral standard of care and 82% using SC N6LS. No participant experienced virologic failure through 12 months, and no clinically significant adverse events were reported after 6 months.

“In totality, these findings support the continued evaluation of the IV formulation, which has been selected to move forward into part 2 of the EMBRACE study, where it will be dosed every 6 months and given along with [CAB LA every 2 months],” Rolle concluded.

Daily Oral BIC/LEN Effective in Those Switching from Complex Regimens

Novel therapies were also given time to shine as Chloe Orkin, MBE, professor of infection and inequities at Queen Mary University in London, presented results from the ARTISTRY-1 study (NCT05502341),³ which is an open-label study that is evaluating the efficacy of switching from a complex regimen to treat HIV to a single-tablet oral regimen of BIC/LEN.

Complex, or multitablet, regimens are less common at present, as most individuals have switched to single-tablet regimens, said Orkin. However, viral resistance, intolerance, and contraindications are among the reasons why individuals living with HIV may need to rely on multitablet regimens, especially in older populations who have picked up these resistances over their decades of being treated. This is where BIC/LEN could be needed.

The phase 3 portion of the ARTISTRY-1 trial focuses on the safety and efficacy of BIC/LEN in those who were already virally suppressed for at least 6 months, had no prior exposure to lenacapavir, had no resistance to bictegravir, did not have hepatitis B infection, and had estimated glomerular filtration rate greater than 50. The primary end point was an HIV viral load of less than 50.

There were 557 participants in this study, of which 371 switched to BIC/LEN and 186 continued their complex regimen. The majority of the participants were men (82.7%) and White (70.1%). The median age of the BIC/LEN group was 60 (range, 22-84) years, which was similar to the median age of the complex regimen group (60 [24-75] years).

“The duration that these participants had taken HIV treatment was just under 30 years, longer than many of the young investigators have been alive,” Orkin joked to the audience’s laughter.

Through 48 weeks, BIC/LEN was found to be noninferior to the complex multitablet regimens, with 96.0% maintaining virologic suppression on BIC/LEN compared with 93.5% who were suppressed on the complex regimen. Only 3 patients in the BIC/LEN group had 50 or more copies/mL through 48 weeks but all 3 resuppressed or had low-level viremia without changing their treatment.

CD4 count remained stable over time in both populations. Adverse events were also similar across the 2 groups, with 82.2% of the BIC/LEN group reporting adverse events compared with 84.4% of the complex regimen group.

“These data suggest that BIC/LEN is an important option, enabling treatment to be tailored for people with viral suppression on complex regimens,” Orkin concluded.

References

1. Rockstroh JK, Kassim S, Paredes R, et al. DOR/ISL (100/0.25 mg) vs BIC/FTC/TAF for initial HIV-1 therapy: week 48 results of phase III study. Presented at: Conference on Retroviruses and Opportunistic Infections 2026; February 22-25, 2026; Denver, CO. Abstract 177.
2. Rolle CP, Luetkemeyer AF, Bettacchi C, et al. Maintenance of HIV suppression at 12 months with VH3810109 (N6LS) Q4M + CAB LA QM: the EMBRACE study. Presented at: Conference on Retroviruses and Opportunistic Infections 2026; February 22-25, 2026; Denver, CO. Abstract 178.
3. Orkin CM, Ruane PJ, Hedgcock M, et al. Phase III efficacy and safety of switch from complex regimen to single-tablet BIC/LEN in ARTISTRY-1. Presented at: Conference on Retroviruses and Opportunistic Infections 2026; February 22-25, 2026; Denver, CO. Abstract 181.