Thigh ART Injections May Open the Door for Self-Injection

Cabotegravir and rilpivirine (cabenuva), the only complete HIV treatment regimen delivered by injection, could be given by intramuscular injection to the thigh rather than the gluteal muscles, research suggests. Currently, the intramuscular injections are provided by healthcare professionals. The new research might make self-injection of this antiretroviral therapy (ART) a more feasible option.

But the study published in Clinical Infectious Diseases by scientists at GSK and ViiV Healthcare only provided a handful of thigh injections to people who had already been receiving gluteal injections of the drugs for over 3 years. Long-term provision of thigh injections would need to be tested in another study before it could be recommended.

For the 118 people with HIV taking part in the study, differences in drug levels following gluteal and thigh injection were not judged to be clinically significant. No participants had HIV-1 RNA ≥ 50 copies/mL after thigh injections.

“We found that peak levels of the medicines in the blood were generally higher one week after thigh injections compared to gluteal injections, especially for those receiving injections every 2 months,” Susan Ford, PharmD, clinical pharmacokineticist at GSK told Medscape Medical News. “This is consistent with faster absorption for thigh administration as compared to gluteal administration.”

Different Absorption Rates

Faster absorption of cabotegravir results in lower steady-state trough concentrations. Population pharmacokinetic modelling conducted as part of the study suggested that if thigh injections were provided in an ongoing manner, they would need to be every month rather than every 2 months in order to maintain efficacious drug levels.

But short-term thigh administration — for example, for patients experiencing injection site fatigue in the gluteal region — would be possible whether the injection schedule is every month, or every 2 months. Both schedules are approved for ventrogluteal or dorsogluteal administration of cabotegravir/rilpivirine.

“The data are really promising in terms of drug concentrations, with most benchmarks being met, and virologic efficacy being on par with what we observed in the phase 3b original clinical trials,” said Lauren F. Collins, MD, MSc, who wasn’t involved in the study. Collins is an assistant professor in the Division of Infectious Diseases at Emory University, Atlanta, Georgia.

Participants were covered by thigh injections for 16 weeks. The 64 participants on a monthly injection schedule had four thigh injections, while the 54 participants on the every-2-months schedule only had two.

As all participants had been taking cabotegravir/rilpivirine for at least 3 years, they probably had a residual accumulation of the drugs in their body before study entry.

“I would feel more confident with longer term data and in different subgroups to be able to offer this more broadly as an option,” Collins said.

She noted that the sample was not especially diverse: 80% were White individuals, 65% were men, and the median age was 48 years. 

Also, the median body mass index (BMI) was 25.4 kg/m² (interquartile range, 23.2-29.7). As there is some concern about suboptimal cabotegravir/rilpivirine concentrations in people who have obesity, including more participants with a high BMI would have been valuable.

In line with prior studies of gluteal injections, pain and other injection site reactions were commonly reported (70% participants). Having tried both injection sites, 30% of participants preferred the thigh, 61% the gluteal muscles, and 9% expressed no preference.

Added Injection Options for Patients

Study injections were provided by healthcare professionals, but the findings may lead the way to further innovations.

“These findings make the promise of self injection more feasible,” Collins said in an interview. “Accessibility of administration site is an absolute must to be able to administer an intramuscular injection to oneself, and so the thigh makes that possible.”

In a study conducted before injectable ART was actually available, 67% of people with HIV told Collins and her colleagues that self-injection appealed to them, while 60% of respondents said they were interested in having a close friend or family member provide the injection.

Medical appointments for ART injections every month or two could be a burden for patients who have got used to 6-monthly check-ups. And healthcare providers may also see benefits, as these visits add pressure to already stretched clinics and staff.

But it doesn’t appear that self-injection would help address disparities. People with HIV who were interested tended to be white and stably housed, with interviews suggesting that stigma and confidentiality concerns would discourage others from bringing injections into the home.

Ford confirmed that GSK and ViiV are continuing to work on alternative injection modalities.

“We’re working toward self-administration and will have a regimen selected in the future,” she said. For the moment, self-administration studies haven’t started, and she indicated that such studies may be of other medications.

The company previously worked on a subcutaneous formulation of cabotegravir/rilpivirine, but development was stopped owing to poor tolerability. 

“Additional study would be required to progress thigh administration further,” Ford said.

Ford is an employee and stockholder of GSK. Collins reported no relevant financial relationships. 

Roger Pebody is a freelance journalist based in Paris, France.