Jose Arribas, MD, on the Challenges That Come With Long-Acting Injectables

The announcement of the results of the FLAIR and ATLAS studies at the Annual Conference on Retroviruses and Opportunistic Infections in March was a major step forward in the field of long-acting injectables for the treatment and management of HIV. But with advances come challenges.

Jose Arribas, MD, head of the Infectious Diseases Unit at La Paz Hospital in Madrid, Spain, sat down with Contagion® at the European Congress of Clinical Microbiology and Infectious Diseases in Amsterdam to discuss the challenges that lie ahead in the development and implementation of monthly long-acting regimens, and also what other treatments are in the pipeline.

Interview transcript (modified slightly for readability):

Contagion®: Long-acting injectables are gaining more ground and showing positive results in studies such as FLAIR and ATLAS. But your presentation is on the challenges of long-acting injectables. Can you explain what the challenges are?

Dr. Arribas: Yes, the results of ATLAS and FLAIR clearly supports the use of long-acting cabotegravir/rilpivirine as monthly intramuscular (IM) injections but there are still challenges with how to implement these strategies in our clinics. The first 1 is who are the best candidates for these therapies. At first sight, it might seem like poorly adherent patients are the best candidates for these indications because when you inject them, you have covered 1 month or perhaps 2 months (when the ATLAS-2M results are released), but it is obviously very important that the patient has to come back to the clinic for the next dosing so you need a safety measure to guarantee that the patient comes back. Because if he or she doesn’t come back, there is a long tail of elimination of these drugs and there is the possibility of resistance. That’s challenge No. 1.

No. 2 is that we work in Europe in very busy clinics and right now with oral therapy, the patient comes to the clinic every 6 months. If they have to come back every month to the clinic for the IM administration, that will put more stress on clinics that already busy. Working in a national public health service, the other issue is going to be cost...We have cheap generics that are oral so still we have to see how we are going to handle the issue of cost. Those are the 3 big challenges right now with monthly intramuscular injections.

Contagion®: Can you discuss the long-terminal half-life of the injections and the risk for resistance?

Dr. Arribas: The issue of the long terminal half-life of these combinations is very important both for treatment and also for prevention. For treatment, we have a window in the trial of 2 weeks for the patient to come back to the clinic for the next dosing. But if the patient doesn’t come back, they need a backup regimen. With the cabotegravir/rilpivirine it’s nice we have the oral formulation of these drugs so if for some reason the patient cannot come back to the clinic, he or she will be able to take the oral medication to cover for this long tail.

With [pre-exposure prophylaxis], this issue is also very important because you can detect this drug—after you stop cabotegravir, for example, you can detect it up to 52 weeks after stopping the drug—in a proportion of patients so we have to cover that tail with oral medication…This is definitely something we need to take into account with this strategy.

Contagion®: What is next for the field of long-acting injectable research?

Dr. Arribas: The next step in research for long-acting is to try and [administer] even more infrequently. What is coming relatively soon is the data from cabotegravir/rilpivirine every 2 months instead of 1 month. There is a pipeline of long-acting drugs that are also looking at other ways. With the drug MK-8591, there is the possibility of even orally once weekly…There is this new family of drugs, capsid inhibitors. The first compound, we’ve seen data at CROI, that can be given in healthy volunteers subcutaneously and, within the pharmacokinetics, probably allowed to give it every 3 months. There is the issue also of implants. With implants, there is the possibility, at least, for some drugs to be used every 6 months or every year. But again, we need to find the partners for these drugs.

The presentation, “Antiretroviral Treatment Challenges: The Future of Long-Acting Formulations,” was presented in a symposium Saturday, April 13, 2019, at ECCMID 2019.