Injectable HIV Prevention Drug Well Tolerated in Early Study

Marcia Frellick

February 25, 2016

BOSTON — The injection of long-acting cabotegravir (ViiV Healthcare) into the gluteal muscles of men at low risk for HIV is a safe and well-tolerated pre-exposure prophylaxis, according to results from the phase 2a ÉCLAIR study.

The data support moving the drug into phase 3 trials, lead researcher Martin Markowitz, MD, from the Aaron Diamond AIDS Research Center in New York City, said here at the Conference on Retroviruses and Opportunistic Infections 2016.

It is well known that the effectiveness of pre-exposure prophylaxis is strongly tied to adherence, so there is great interest in developing a long-acting injectable for HIV prevention, said Albert Liu, MD, from the Department of Public Health in San Francisco, who was not involved in the ÉCLAIR study.

"This approach could help address challenges with adherence to daily oral pre-exposure prophylaxis and provide options for those who prefer not to take a daily pill," he told Medscape Medical News.

"The ÉCLAIR study provides important data on the safety, tolerability, and acceptability of cabotegravir LA in HIV-uninfected men. These data, along with data from the HIV Prevention Trials Network 077 study currently under way, will help pave the way for a phase 3 evaluation of efficacy," Dr Liu explained. "The pharmacokinetic data from ÉCLAIR are also critically important, as they suggest that more frequent dosing — every 2 months — may be needed to achieve optimal levels for protection."

There is great interest in developing a long-acting injectable for HIV prevention.

The absorption rate of the drug was higher than predicted, so the peaks were higher and the troughs were lower after each injection than the researchers anticipated, Dr Markowitz reported. That indicates the likely need to change the dosing from 600 mg once every 12 weeks to once every 8 weeks, he pointed out.

ÉCLAIR study

The trial involved healthy men 18 to 65 years of age who were considered to be at low risk for HIV infection. Participants were randomized in a 5:1 ratio to cabotegravir, an investigational integrase strand transfer inhibitor formulated in a long-acting suspension, or placebo.

There were three phases in the study: an oral phase, an injection phase, and a follow-up phase. Safety was assessed after the month-long oral phase, during which participants received oral cabotegravir daily or placebo. If the participants were clinically stable, they moved on to the injection phase, which meant an injection in the buttocks every 12 weeks, for a total of three injections.

One week after each injection, patients completed a questionnaire and submitted diaries containing detailed information on injection-site reactions.

From these data, the researchers determined that injection-site reactions were much more common in the cabotegravir group than in the placebo group (272 vs 62 reactions).

92% of the cabotegravir injections were associated with complaints of pain.

"It's really interesting to note, and a little bit surprising, that the actual act of injecting saline elicited complaints of injection-site pain in 27% of subjects that lasted approximately 2 days," Dr Markowitz said. This suggests that "some injection pain is caused by the act of injection. That said, 92% of the cabotegravir injections were associated with complaints of pain."

About half the patients said the maximum intensity of pain was mild, 40% said it was moderate, and 10% rated it grade 3. Other injection-site effects, such as itching and swelling, were rare, he reported.

However, "of the 94 subjects who entered the injection phase, only seven discontinued therapy," and only four of these discontinuations were related to injection intolerability, Dr Markowitz said.

It is hard to evaluate pain as an adverse event because it is so subjective, he told Medscape Medical News. "That's an enormous variable and a limitation of the study."

During the injection phase, no drug-related laboratory abnormalities led to the discontinuation of therapy, he added.

Dr Markowitz reports that his institution received research grants from GSK/ViiV and Gilead Sciences, and that he has served as a consultant for Merck and as a speaker for Gilead Sciences. Dr Liu reports receiving support from Gilead Sciences for studies he has conducted.

Conference on Retroviruses and Opportunistic Infections (CROI) 2016: Abstract 106. Presented February 24, 2016.


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