One year into offering the first long-acting injectable HIV treatment to his patients, Jonathan Angel, MD, head of the Division of Infectious Diseases at the University of Ottawa, Ontario, Canada, reported that 15 of the 21 of patients who started on the regimen are still taking it, all with viral suppression. Those who weren’t cited a combination of inconvenience, injection site pain, and “injection fatigue.”
These are just a few things HIV providers are learning as they begin what Chloe Orkin, MD, professor of HIV medicine at Queen Mary University of London, United Kingdom, called a paradigm shift to long-acting treatment, which may soon include not just shots but rings, implants, and microarray patches.
“It’s a paradigm shift, and we are at the very beginning of this paradigm shift,” said Orkin, commenting during the discussion session of the European AIDS Clinical Society (EACS) 2021 Annual Meeting. “We’re having to change our model and it’s challenging.”
In the United States, the U.S. Food and Drug Administration approved the first long-acting injectable, a combination of cabotegravir and rilpivirine (CAB/RIL; Cabenuva, ViiV Healthcare) in January 2021. But it has been approved in Canada since March 2020 and available at Angel’s clinic since November 2020. It’s also available in Canada as an every-other-month shot. Injected into the buttocks, the shot was found to be nonnferior to standard daily oral treatment in many studies, including the ATLAS, the ATLAS-2M — which tested the every-other-month approach — and FLAIR trials.
Angel’s clinic was part of all three of those trials, so his clinic has had 5 years’ experience preparing for the change in workflow and the new approach the shots require.
Of the 21 people Angel has treated, 11 were white Canadians, nine were Black African, and one was Indigenous Canadian, with women making up a third of the participants. Median age was 51 years, and all patients had had undetectable viral loads before beginning the regimen. (Studies of the drug’s effectiveness in people who struggle to take daily pills are still ongoing.)
Most of those 21 patients had had undetectable viral loads for more than 5 years, but a few had been undetectable for only 6 months before beginning the shots. Their immune systems were also healthy, with a median CD4 count of 618 cells/µL. As in the clinical trials, none of the participants had experienced antiretroviral treatment failure. Because public health insurers in Canada have yet to approve the shots, Angel’s patients receiving Cabenuva also have private health insurance. Up to 90% of people in Canada receive pharmaceutical coverage through public insurance; therefore, the shot is not yet widely available.
Twenty patients switched from integrase inhibitor regimens, and one had been receiving a non-nucleoside reverse transcriptase inhibitor–based regimen before starting Cabenuva.
And although the drug has not been approved for shot initiation this way, two patients requested — and Angel agreed — to start them on the shots without first doing a month of daily pills to check for safety.
“This is my conclusion from these data: the oral lead-in period is not necessary,” Angel said in his presentation at the meeting. “It can provide some comfort to either a physician or a patient, but it does not seem to be medically necessary.”
That approach is not without data to back it up. Research presented at HIV Glasgow 2020 showed that people who switched from daily oral dolutegravir/abacavir/lamivudine straight to the injections did so without problems.
At last clinic visit, 15 of those 21 were still receiving the shots. None have experienced treatment failure, and all were still virally suppressed. Four participants left the trials and one more person opted to return to daily pills, citing some level of what Angel called “injection fatigue.”
“Just as we use the term ‘pill fatigue’ for patients who are tired of taking pills, patients do get tired of coming in monthly for their visits and injections,” he said. They find the trip to the clinic for the intramuscular injections “inconvenient,” he said.
Unlike in the United States, where Cabenuva is approved for only monthly injections, Health Canada has already approved the shot for every-other-month injections, which Angel said may reduce the odds of injection fatigue.
Angel’s presentation drew comments, questions, and excitement from the crowd. Annemarie Wensing, MD, assistant professor of medicine at University Medical Center Utrecht, the Netherlands, asked whether dispensing with the oral lead-in period could mean that these shots could be useful for people going on longer trips, people having surgeries where they can’t swallow pills, or in other scenarios.
“These are not hypothetical conversations,” Angel said. “I’m having these conversations with patients now — temporary use, they travel for 3 months and come back, can they go from injectable to oral to injectable.”
For now, he said, the answer is, “We’ll figure it out.”
Meanwhile, there’s another big question when it comes to injectables, said Marta Vasylyev, MD, from Lviv Regional AIDS Center in Ukraine: when will they be available to the people who might benefit most from them — people in resource-limited settings, people who so far have struggled to remember to take their pills every day?
For now, Angel replied, injectables continue to be a treatment only for those who are already doing well while receiving HIV treatment: those with already suppressed viral load, who are good at taking daily pills, and who are being treated at well-resourced clinics.
“There are huge obstacles to overcome if this is ever to be available [in resource-limited settings], and way more obstacles than there are with any oral therapies,” he said. “There’s not been much discussion here about the necessity of cold-chain requirements of pharmacies either centrally or locally, [or] the requirements of additional nurses or healthcare staff to administer the medication. So you’re looking at a very resource-intensive therapy, which now is fairly restrictive [as to] who will have access to it.”
Angel reports serving on advisory boards for ViiV Healthcare and Gilead Sciences and has done contract research for ViiV Healthcare, Gilead, and Merck. Orkin has received research grants, fees as a consultant, travel sponsorship, and speaker fees from ViiV, Merck, and GlaxoSmithKline. Vasylyev reported no relevant financial relationships.
European AIDS Clinical Society (EACS) 2021 Annual Meeting. Parallel Session ACT NOW. Presented October 29, 2021.
Heather Boerner is a science journalist based in Pittsburgh, Pennsylvania. Her book, Positively Negative: Love, Pregnancy, and Science’s Surprising Victory Over HIV, came out in 2014.
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