Treatment with the single-tablet regimen (STR) doravirine/islatravir (DOR/ISL; 100/0.25 mg) results in sustained virologic suppression in almost all virologically suppressed adults with HIV-1 receiving complex antiretroviral therapy (ART) regimens, a study has shown.
DOR/ISL is efficacious even in participants with resistance to nucleos(t)ide reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), or integrase strand transfer inhibitor (INSTI). The STR is also well-tolerated through week 48.
“DOR/ISL may provide a simplification strategy for people with HIV-1 who are currently receiving a complex ART regimen,” said presenting author Dr Michelle Fox, Merck & Co, Inc, Rahway, US.
“DOR/ISL once daily has demonstrated noninferior efficacy in both virologically suppressed and previously untreated adults with HIV-1 and has a safety profile similar to the comparator ART regimens,” she added. [Lancet 2026;407:611-621; Lancet 2026;407:599-610; Lancet HIV 2026;13:e440-e451]
Fox and colleagues randomized adults with HIV-1 RNA <50 copies/mL for ≥3 months on oral 2- or 3-drug ART, with no history of treatment failure or known resistance to DOR, in a 2:1 ratio to switch to DOR/ISL or continue baseline ART (bART). ART regimens containing ≥2 pills per day were deemed complex.
On day 1, 57 of 366 participants (15.6 percent) switched to DOR/ISL, and 27 of 185 (14.6 percent) continued a complex regimen in the bART group. Baseline characteristics were comparable between the two treatment groups. [AIDS 2026, abstract LB23]
Efficacy
Participants receiving complex regimens had longer time to HIV-1 diagnosis, longer duration of prior ART, and tended to be older, male, on ≥4th ART regimen, and on a protease inhibitor- or NNRTI-based regimen compared with their counterparts on STRs.
Polypharmacy, defined as five or more non-ART medications, was more common among participants on complex prior ART than those on noncomplex prior ART (36.9 percent vs 26.3 percent).
At week 48, virologic outcomes did not significantly differ between the DOR/ISL and bART groups, with HIV-1 RNA <50 copies/mL maintained in 96.5 percent and 96.3 percent of participants, respectively. Of the 57 individuals who switched to DOR/ISL, 31 (54.4 percent) had NRTI, NNRTI, and/or INSTI resistance-related mutations in proviral DNA at baseline, and 30 (96.8 percent) remained virologically suppressed.
The mean change from baseline in CD4+ T-cell count at week 48 was ‒18.1 cells/mm3 (95 percent confidence interval [CI], ‒54.3 to 18.2) in the DOR/ISL group and 33.3 cells/mm3 (95 percent CI, ‒61.5 to 128.2) in the bART group (treatment difference, ‒44.8 cells/mm3, 95 percent CI, ‒135.6 to 46.0).
Safety
Among participants with complex prior ART, the incidence of treatment-related adverse events (AEs) was higher in the DOR/ISL group than in the bART group (12.3 percent vs 0.0 percent; difference, 12.3 percent, 95 percent CI, ‒0.8 to 23.3).
The incidence of grade 3/4 AEs did not significantly differ between treatment groups (8.8 percent vs 7.4 percent; difference, 1.4 percent, 95 percent CI, ‒15.6 to 13.3). None were related to the study regimens. Furthermore, serious AEs occurred in the DOR/ISL group but not in the bART group (7.0 percent vs 0.0 percent; difference, 7.0 percent, 95 percent CI, ‒5.9 to 16.8), and none were treatment-related.
None of the participants in either group died or ceased treatment due to an AE.
“DOR/ISL is a new STR … that is available in the US and Japan to replace the current ART regimen in adults with HIV-1 who are virologically suppressed with no history of virologic treatment failure and no known substitutions associated with resistance to DOR,” Fox said.
“STRs have been the standard of care for HIV-1 treatment for almost 2 decades, [but] many people with HIV require more complex regimens due to intolerance, drug‒drug interactions, drug resistance, or contraindications to existing STRs,” she noted.