Doravirine combinations noninferior for maintaining viral suppression in adults with HIV
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SEATTLE — Doravirine was noninferior at maintaining viral suppression in people with HIV through 48 weeks when compared with bictegravir/emtricitabine/tenofovir alafenamide, as well as baseline ART.
Researchers presented these findings at the Conference on Retroviruses and Opportunistic Infections.
The first of the studies presenting data on doravirine (DOR) was presented by Anthony M. Mills, MD, an HIV specialist and CEO of the Men's Health Foundation.
Mills and colleagues performed a double-blind, active-controlled study, during which 643 adults with HIV-1 RNA less than 50 c/mL for 3 months or longer on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) without history of treatment failure were randomly assigned 1:1 to switch to DOR and islatravir (DOR/ISL), or continue with B/F/TAF.
The primary efficacy endpoint was the percentage of participants with HIV-1 RNA 50 c/mL or more at week 48.
In total, 322 participants switched to DOR/ISL, whereas 319 continued B/F/TAF. At week 48, two participants on DOR/ISL and one on B/F/TAF had HIV-1 RNA 50 c/mL or more (difference 0.3; 95% CI, –1.2 to 2), which the researchers said demonstrates noninferiority, whereas HIV-1 RNA was less than 50 c/mL in 93.8% of participants on DOR/ISL and 94.4% of participants on B/F/TAF. Additional study data showed that one participant who received DOR/ISL had clinically significant confirmed viremia (CSCV) at week 12.
According to the study, rates of adverse events (AEs) and drug-related AEs were similar between groups — 71.1% among DOR/ISL recipients vs. 74.6% among B/F/TAF recipients and 9.9% vs. 11.9%, respectively. Both groups saw discontinuation rates of 2.5% because of AEs, with the most common AE in both groups being headache (7.8% DOR/ISL vs. 7.2% B/F/TAF).
Additional data from another phase 3 study of DOR presented at the Conference on Retroviruses and Opportunistic Infections by Jean-Michel Molina, MD, PhD, professor of infectious diseases at the University of Paris, showed that switching to DOR from baseline ART (bART) was also effective at maintaining viral suppression at 48 weeks.
According to the study, virologically suppressed adults on any stable oral two- or three-drug ART for 3 months or longer with no history of treatment failure or virologic resistance to DOR were randomly assigned 1:1 to switch to DOR/ISL or continue bART. The primary endpoint was finding the percentage of participants with HIV-1 RNA 50 c/mL or more at week 48.
In total, 672 participants were randomly assigned and treated with DOR/ISL (n = 336) or bART (n = 336). Participants treated with bART were stratified by type, with 14% receiving protease inhibitor-based bART, 52% integrase strand transfer inhibitor (InSTI)-based bART and 34% receiving other forms of bART, which were mainly non-nucleoside reverse transcriptase inhibitor (NNRTI) based.
The study showed that at week 48, 0% on DOR/ISL and 1.5% on bART had HIV-1 RNA 50 c/mL (95% CI, –3.4 to –0.3), whereas 95.2% on DOR/ISL and 94.3% on bART had HIV-1 RNA less than 50 c/mL.
CSCV occurred in three participants on bART — one of whom received lnSTI-based bART and two who received nucleoside reverse transcriptase inhibitor-based bART. Researchers added that all three had resistance to one component of their regimen.
According to the study, rates of drug-related adverse events (AEs) (19.6%, 8.9%) and discontinuation because of AEs (2.1%, 0.3%) were higher in the DOR/ISL group — 19.6% vs. 8.9% and 2.1% vs. 0.3%, respectively — whereas rates of grade 3 to 4 AEs and serious AEs were similar between the groups — 6.8% vs. 7.4% and 4.2% vs. 3.9%, respectively.
“One size doesn't fit all,” Molina said during a press conference. “But what's good about these new combinations and these new treatment strategies is that it gives people multiple options.”
He told Healio that the duel combination of DOR, an NNRTI, and ISL was noninferior and “looks promising” but should be assessed using a lower dose of ISL in the future.
Mills AM, et al. Abstract 197. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 19-22, 2023; Seattle.
References:
- Molina JM, et al. Abstract 196. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 19-22, 2023; Seattle.
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Mills AM, et al. Abstract 197. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 19-22, 2023; Seattle.
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