HIV trial participants remain virally suppressed on dolutegravir monotherapy
Click Here to Manage Email Alerts
Key takeaways:
- Dolutegravir monotherapy was safe and noninferior vs. combination ART.
- Switching to monotherapy from combination ART allowed patients to achieve sustained virological suppression.
patients with HIV who initiated combination ART early after their infection continued to remain virally suppressed 96 weeks after they were switched to dolutegravir monotherapy, according to data from the EARLY-SIMPLIFIED study.
“For decades, we treated people with HIV (PWH) alike, meaning that pretty much everybody was treated with triple therapy. We know, however, that there are quite some differences between individuals,” Dominique L. Braun, PD Dr. med, senior staff physician at the University Hospital Zurich, and Huldrych Günthard, MD, deputy director of the University Hospital Zurich’s division of infectious diseases and hospital epidemiology, told Healio.
“We and many others have done a lot of work in the past to better characterize the latent reservoir. We have particularly also focused on PWH who have been diagnosed during an acute or recent HIV infection,” they said.
Braun and Günthard explained that these people have been enrolled in the Zurich Primary HIV infection, which has showed numerous times that if PWH are treated early after infection, the latent reservoir is approximately 10 times lower when compared with chronically infected PWH.
“Thus, our hypothesis was that people treated early after infection (during primary HIV infection) with a low viral reservoir could potentially be switched from a standard triple combination ART (cART) to dolutegravir (DTG) monotherapy,” they said.
Braun, Günthard and colleagues conducted a 4-year study called EARLY-SIMPLIFIED meant to determine whether simplification of cART to DTG monotherapy would allow sustained virological suppression to take place.
According to the study, PWH who started cART less than 180 days after a documented primary HIV infection with suppressed viral load were randomly assigned 2:1 to DTG monotherapy with 50 mg daily (n = 68) or continuation of cART (n = 33). The primary endpoints of the study were the proportion of PWH with viral failure at 48, 96, 144 and 192 weeks.
In total, 101 PWH were randomly assigned — 68 of whom assigned to DTG monotherapy and 33 to cART. The study demonstrated that at week 96, 100% of patients in either group showed virological response, demonstrating noninferiority of DTG monotherapy at the prespecified level.
Additional data from week 192 demonstrated that no virological failure occurred in either group during 13,308 and 4,897 person weeks of follow-up for the DTG monotherapy and cART groups, respectively.
Safety data collected during the study showed that of the 68 patients in the DTG monotherapy group, 17 (25%) experienced serious adverse events compared with 10 (30.3%) of the 33 on cART, while drug-related adverse events were seen in 15 out of 68 (22.1%) patients on DTG monotherapy and 10 out of 33 (30.3%) on cART. According to the study, ART regimen change because of an adverse event was significantly more frequent in the cART group (15.2%) vs. the DTG monotherapy group (1.5%).
“In principle, this study shows that a considerable fraction of PWH could probably be switched to DTG monotherapy. Thus, in principle, we could do targeted precision medicine for HIV treatment,” Braun and Günthard said. “This means that a lot of costs, but also long-term toxicity, could potentially be avoided.
They added, however, that larger, randomized clinical trials would be needed to define the threshold of the latent reservoir at which one could switch to DTG monotherapy.
“Currently, although highly successful, our study does not allow yet to put people on DTG monotherapy outside of well-controlled studies,” Braun and Günthard said, echoing the conclusion of the study, which says the researchers "see no widespread indication for DTG monotherapy."
"However, we believe our study contributed to existing evidence that triple-ART represents over-treatment of HIV infection in a significant proportion of patients," they wrote. "We hope to pave the way for additional work to reduce ART-burden by patient stratification according to latent reservoir size or duration of active infection before starting therapy."
Collapse
West E, et al. Clin Infect Dis. 2023;doi:10.1093/cid/ciad366.
Read more about
Click Here to Manage Email Alerts