Long-Acting Injectables in the HIV Treatment Landscape


The role of and indication for long-acting injectables is highlighted as a treatment approach for HIV.

Adam C. Welch, PharmD, MBA: An evolving space is long-acting injectables. It sounds great: 1 injection, and a patient is covered for a period of time, even months. But that’s not always the case. Talk a little about long-acting injectables.

Christian B. Ramers, MD, MPH, FIDSA, AAHIVS: This is an exciting and evolving area. You’ve heard us mention adherence often, and it’s critical for a patient to have almost perfect adherence, or at least good enough to keep the virus suppressed. Here’s another way to almost guarantee that you have very good adherence, as long as the patient receives the injection in time. There are a couple of products already on the market and a very rich pipeline of things to come.

The first I’ll mention is something called Cabenuva [cabotegravir, rilpivirine]. It’s long-acting injectable cabotegravir paired with long-acting injectable rilpivirine. This isn’t 1 of the regimens recommended to start with. It’s only for patients who have been in care and have their virus already suppressed. That’s typically how things get introduced into the guidelines. In the future, there may be the introduction of this into the first 4 or 5 regimens that recommended. The way it is now, you get a patient started and give an oral version of the injectable first if you want to, but you don’t have to. Then switch to the injectables, which can happen a couple of months in a row and then every 2 months. The patient has to come into the office. It has to be administered by a health care provider and get an injection. Then they don’t have to think about a pill for the next 60 days. Patients who have been in the clinical trials that have led to the approval, and also my patients who are on it, appreciate not having to remember that pill every day. If you witness that injection, you have 100% adherence automatically. That gets over 1 of our major challenges in HIV therapy.

The cabotegravir part of that dual regimen that’s approved for HIV treatment is also licensed for prevention. It’s a little outside the box, but through the prevention work we’ve done in the last 10 to 15 years, the concept of providing somebody an HIV medicine to prevent them from getting infected has gained ground—but not enough ground. Since 2012, a medicine called Truvada [emtricitabine, tenofovir] has been approved and recommended to take orally for individuals who are HIV negative but at risk. We’ve talked about how expensive and burdensome every 1 of those 30,000 HIV infections is. If we can prevent even 1 of them, it saves the system money.

Taking that and moving it into an injection, the 1 Achilles’ heel of prevention is adherence. In all the trials that have been done looking at Truvada and Descovy [emtricitabine, tenoforvir alafenaminde] as another prevention medicine, the patients it doesn’t work for are the ones who can’t remember to take that pill every day or have poor adherence. You solve that problem by having a witnessed injection. That long-acting cabotegravir, brand-name Apretude, is now available as a preventive medicine that you can give every 2 months. It’s very effective. In fact, it was superior to the oral prevention medicines in the clinical trials. It’s an evolving area. There isn’t an ideal patient. Some payers worry that this is a brand-new shiny toy and that everyone is going to just rush the pharmacies and jump on it. But I have patients who are comfortable with their oral pills, and they don’t quite want to switch to injections. Maybe 10% of my patients who are stable say, “I want to try this.” It’s a different way of doing it.

It’s a different burden of care because they have to come in every 2 months. There’s additional blood testing that has to be done, as opposed to someone who’s stable and doing well. They take their pills and come in every 6 months or so. But it’s an expanding option. We’re well aware of pipeline options that can go even longer. The holy grail or the desired effect is to have an injection that lasts even longer, maybe 6 months. There are individuals working on implants [that would be like those] for hormonal contraception. They would be reversible implants under the skin that use just a little of the drug. Using that in treatment and prevention is the future.

Adam C. Welch, PharmD, MBA: Unlike hypertension, diabetes, and other chronic medical diseases, we don’t use terms like treatment naïve or treatment experienced when we’re talking about those diseases. But we do with HIV, and that becomes important. Talk to me a little about what it means when you’re starting therapy vs a patient with HIV who’s been on therapy and has more treatment experience.

Ann Khalsa, MD, MSEd, FAAFP, AAHIVS: The words refer to a history of ever taking medications. You’re naïve to treatment if you’ve never taken HIV meds before. Usually, you have your best success rates in terms of attaining or achieving viral suppression in treatment-naïve trials. Historically, in the beginning, we were happy if we got 60% of patients suppressed with a triplet regimen, not even the old dual and single regimens. Now our expectation is well above 90% effectiveness. These meds work. That’s the bottom line. It’s same with hepatitis C—similar history but different story.

Treatment experienced are patients who’ve taken other regimens before. The Achilles’ heel is that there’s resistance to past regimens. This occurred historically because we didn’t have fully active triplet regimens for the first 2 decades. It took awhile to learn to do therapy in a way that prevented resistance to the virus. We have routine treatment-experienced trials where someone is on an initial regimen. Let’s say they were on Biktarvy [bicregravir, emtricitabine, tenofovir alafenamide] and they want to try Cabenuva, and they’ve been successful on Biktarvy with no resistance. It’s a suppressed switch trial that’s going to be similar to a treatment-naïve trial because there’s no resistance. Then you have the highly treatment-experienced who’ve had resistance in various classes. You have to be much more creative, thoughtful, and thorough in your assessment of their resistance to find an effective regimen you can still treat them with.

Adam C. Welch, PharmD, MBA: Shauna, talk to me a little about someone who is treatment-naïve. You can test to see if they’re going to be resistant to certain therapies. You can provide some genetic testing. Talk to me about the testing prior to initiating therapy.

Shauna Applin, ARNP, CNM, AAHIVS: The testing itself is the same test we can use once they’re already experienced, but we’re doing what we call baseline resistance testing. It looks at the concept brought up. Did you already acquire a resistant virus? It’s a baseline test that looks for mutations that would help guide us in choosing a fully active regimen for someone who’s never been on treatment. This similar concept is called acquired resistance vs transmitted resistance vs something that I did to myself due to lack of adherence. But the testing is very similar, and the outcome is similar in that it helps guide us to choose therapy that’s fully active, whether they’re naïve or already experienced with HIV meds.

Adam C. Welch, PharmD, MBA: It makes sense from a financial standpoint and a health outcome standpoint to support this testing prior to initiating therapy.

Alina Orozco, RN: Absolutely. Why would you go down that road and not make sure the treatment you’re going to be paying for is going to work?

Ann Khalsa, MD, MSEd, FAAFP, AAHIVS: Unfortunately, there are caveats with that kind of testing. That resistant virus has a selective advantage to live in the presence of those drugs because they’re not suppressing the virus. The virus is resistant to it. But if you’re not on those meds, those resistant strains tend to fade. They become part of the background, and you may not find them. If someone has been HIV positive for 5 years and never came into care, and now they’re sick with AIDS or advanced HIV and they need treatment, I can do a resistance test at that time, but it’s not going to be superinformative. Similarly, if I have someone who’s in and out of care for whatever reason, and they’ve been off meds for several months, I’ll typically start them on their last prior regimen and then do a resistance test a month on that regimen to find if they have resistance against the meds I restart them on. That resistance will have faded in the background, so I may not find it. So this also requires a little expertise and experience in treating HIV.

Christian B. Ramers, MD, MPH, FIDSA, AAHIVS: This brings in some of these tricks of the trade that we use. It’s hard to make rigid guidelines that bring in this wisdom. It frustrates us as treaters. When we get a denial, for example, we want to send a specific resistance test. These aren’t cheap tests. The archive resistance tests involve a full laboratory procedure to find that virus. But it’s an amazing technology that allows us to provide optimal care to our patients and not go down a pathway of a drug that’s not going to work. It’s frustrating when those tests don’t get covered because we feel as if we have the expertise to make those good decisions in our patients’ best interests.

Adam C. Welch, PharmD, MBA: It doesn’t fit into a cookie-cutter guideline. The real-world experience that you were seeing every day is crucial to better health outcomes.

Shauna Applin, ARNP, CNM, AAHIVS: The theme you hear from us in each category is to not make shortsighted decisions on the front end for cost that will create more cost in the long run. That’s a great example. If I can’t do this resistance test, and I pick a regimen that’s going to further their resistance, that’s an additional cost to that patient and the system.

Transcript edited for clarity.

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