SEATTLE – Long-acting cabotegravir and rilpivirine coformulated as a monthly injection was non-inferior to a standard daily oral regimen in suppressing HIV viral loads to undetectable levels, according to results from two trials presented here.
Moreover, nearly all participants receiving the injections said they were preferable to the daily pill.
Results of the multinational ATLAS and FLAIR trials were reported at the annual Conference on Retroviruses and Opportunistic Infections. Cabotegravir is an investigational HIV integrase inhibitor under development by Viiv Healthcare; rilpivirine (Edurant) is a non-nucleoside reverse transcriptase inhibitor, currently marketed as a daily pill by Janssen.
The trials’ designs were similar but the study populations differed. In ATLAS, experienced patients agreed to be randomized to either continuation on their current oral regimen or switching to the once-a-month injection; the FLAIR trial was conducted among HIV-infected patients who were naive to treatment with antiretroviral therapy.
In ATLAS, 92.5% of the 308 patients on the monthly injection achieved undetectable viral loads (<50 copies/mL) at 48 weeks compared to 95.5% of the 308 patients taking the oral daily regimen, a difference that fell well within the pre-specified 6% differential for proving non-inferiority, reported Susan Swindells, MBBS, of the University of Nebraska Medical Center, Omaha.
“The patients had to have been stable on their regimen, so ATLAS was basically a switch study, and there were very few treatment failures,” Swindells said in a press conference.
In FLAIR, 93.6% of the 283 patients on the monthly injections achieved undetectable viral loads at 48 weeks compared with 93.3% of the 283 patients who were on oral HIV maintenance therapy, also clearly showing non-inferiority, said Chloe Orkin, MD, of Barts Health NHS Trust, London.
“The primary and secondary endpoints for the trial were met,” she said. “The treatment was well tolerated, and the discontinuations were mainly from non-injection reasons.” She said that the patients seemed to be satisfied with the injection of the drugs, although there were some concerns about development of transitory nodules at the injection site. These nodules usually lasted about 3 days and resolved within a week.
“These studies have the potential to change the way we treat our patients,” said press conference moderator Joseph Eron, MD, of the University of North Carolina, Chapel Hill. “These studies did not take a long time to accrue. People were very interested. The researchers didn’t have to go around and beat the bushes to find people for the study.”
Both studies conducted surveys designed to elicit how well the patients took to the monthly injections, and in both studies there was overwhelming – more than 90% – satisfaction with the injections.
“We were somewhat surprised that the patients preferred getting their medication by injection rather than by taking a pill,” Swindells said.
“These injections are done at the healthcare facility,” she told MedPage Today. “The treatment failures were often among people with HIV who had a different subtype of the disease, the so-called A subtype, and some resistance mutations.” That subtype is often found in Russia where many of the patients in the study were recruited. The same resistance patterns were reported by Orkin in FLAIR, with the A subtype observed in the three cases of virologic failure.
“The patients have a 7-day window in which to get their next injection,” Orkin told MedPage Today. “This is a major paradigm shift in how we administer HIV medication.”
She noted that monthly treatments in other settings are the norm: in psychiatry, for example, with depot injections of antipsychotics, and long-acting hormonal contraception. “So this type of monthly treatment can be done, it’s just that we haven’t done it that way yet and it will require some thought in how to do it” in the HIV treatment setting.
Swindells noted that the open-label study was randomized so patients could not be certain at enrollment whether they would be assigned to the pill or the injection. “My patients tell me that they just like the idea that they don’t have to worry about taking their pills every day; they aren’t reminded every day that they have HIV; they don’t have to worry about their co-workers seeing them with a bottle of pills,” Swindells said.
Orkin, too, said her patients have told her they like the idea of 12 treatment days per year instead of 365.
Eron, who had also conducted clinical trials with cabotegravir and rilpivirine but was not a participant of the ATLAS or FLAIR trials, told MedPage Today, “I think that younger patients who haven’t been on medications and don’t want to carry around pills are willing to consider injections.
“The biggest struggle for me will be to have to avoid my own preconceptions in how I talk to my patients about the medications because I, personally, am not a fan of injections,” Eron said. “I’d rather take a pill. But there are people who just can’t seem to take the pills, and a day doesn’t go by in my clinic in which people ask me when the injectables are going to be available. We should have a decision from the Food and Drug Administration on approval by the end of the year.”
It might not happen that quickly, however. Viiv Healthcare, which is developing the injectable combination, has not yet filed a marketing application. “We look forward to submitting applications to regulatory authorities later this year,” according to a company statement issued Thursday.
The trials were sponsored by ViiV Healthcare.
Eron disclosed relevant relationships with Merck, Panacos, GlaxoSmithKline, Avexa, Bristol-Myers Squibb, Tibotec Therapeutics, Virco, Trimeris, Pfizer, and Roche Laboratories.
Orkin disclosed relevant relationships with Gilead Sciences, Janssen Therapeutics, ViiV Healthcare, and MSD.
Swindells disclosed relevant relationships with ViiV Healthcare and Merck.