Cabenuva is a complete, injectable antiretroviral therapy (ART) regimen for the treatment of HIV. It was approved for use by the U.S. Food and Drug Administration (FDA) in 2021.
How is Cabenuva taken?
Cabenuva is taken as an intramuscular injection once a month, administered by a licensed medical professional. The two medications are given as two injections at separate buttock (gluteal) injection sites—either at opposite sides or at least 2 cm apart on the same side.
What are the drugs in Cabenuva?
Cabenuva is a combination of two intramuscular-injection medications, cabotegravir (CAB) and rilpivirine (RPV):
Cabotegravir is in a class of drugs called integrase strand transfer inhibitors (INSTIs), which stop HIV from making copies of itself later in its life cycle.
Rilpivirine is in a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which block HIV from making copies of itself early in its life cycle.
Does Cabenuva have any side effects I should worry about?
Cabenuva is generally well-tolerated, with the major side effect reported being local pain and irritation at the injection sites.
Cabenuva is a combination medication that was approved for the treatment of HIV in early 2021 by the U.S. Food and Drug Administration (FDA) specifically for people who are already on a stable antiretroviral therapy (ART) regimen and have no history of treatment failure or resistance to the two medications within Cabenuva, cabotegravir and rilpivirine.
A Cabenuva prescription comes as two bottles, one containing a liquid form of cabotegravir and one containing a liquid form of rilpivirine.
Cabotegravir is the newest medication in the integrase inhibitor (INSTI) class of HIV treatment. In addition to its availability as an intramuscular injection as part of Cabenuva, an oral tablet form (brand name: Vocabria) was FDA-approved in 2021.
The rilpivirine component of Cabenuva was first FDA-approved in 2011 as an oral medication with the brand name Edurant. It is also found in two single-tablet regimens: Complera, where rilpivirine is combined with emtricitabine (Emtriva) and tenofovir disoproxil fumarate (Viread); and Odefsey, where it is combined with emtricitabine and tenofovir alafenamide (TAF).
When a person is first prescribed Cabenuva, instead of receiving an injection in their first month, they instead take daily doses of oral Vocabria and Edurant. This is called a "lead-in dose" that ensures your body is ready for Cabenuva injections.
What’s the Big Deal About Cabenuva as an HIV Treatment?
Research and scientific advancement are taking us to places we have never seen before with HIV treatment regimens. In 2017, Juluca (a combination of two other HIV drugs, dolutegravir and rilpivirine) was approved by the FDA as the first two-medication single-tablet regimen (STR) that could be used for HIV treatment. This was a landmark moment, as the standard of HIV treatment since 1997 had been at least three active medications.
Now, with Cabenuva, we have a two-medication regimen that isn’t even a tablet. Cabenuva is the first once-monthly, long-acting injectable HIV treatment regimen: It reduces treatment dosing from a daily pill taken 365 days a year to two injections given by a health care provider once every month.
For those of us old enough to remember the days of people living with HIV having to take 20 pills a day, two to three times a day, with horrific side effects—this progression in how HIV treatment is administered is nothing short of extraordinary.
However, it’s important for both clinicians in the field and for our communities to realize that not only is this a new regimen that is only recently approved, but it involves a new method by which we are delivering medications. This is the first time in 40 years that a complete injectable ART regimen will be an option for people living with HIV, so there will be many logistical considerations to work out. We need to make sure this novel medical advancement can be accessed by all persons in an equitable and efficient fashion.
There may be some expected bumps in the road during the initial rollout, but the big picture of what this progress means for the future of HIV treatment moving forward cannot be overstated.
How Does Cabenuva Compare to Traditional Oral HIV Therapies?
Cabenuva has been studied extensively, both in direct comparison to traditional oral ART regimens as well as in switch studies for people who were on oral ART therapies and changed to this long-acting injectable regimen.
Results from a study published in the New England Journal of Medicine showed that after 48 weeks (almost a year), 92.5% of participants who switched to Cabenuva kept their viral load undetectable (fewer than 50 copies/mL), compared to 95.5% of people who continued their oral regimen. In research jargon, that means that Cabenuva showed it was “noninferior” to the standard of care oral HIV treatment regimens—in other words, it will work just as well in maintaining an undetectable viral load. Additionally, combined analysis (“pooled” data) from two different studies that were published in the journal JAIDS showed that monthly, injectable, long-acting Cabenuva was just as effective at maintaining an undetectable viral load as standard oral therapy.
In another study published in The Lancet, researchers found that, after 48 weeks, Cabenuva injectable treatment was equally effective (“noninferior”) at keeping a person’s viral load undetectable when administered every eight weeks as it was every four weeks. So, although Cabenuva is not currently FDA-approved for use every two months, there may be a time in the near future when this may be an option for people living with HIV. This would further reduce the number of treatments a year from 12 down to six.
In October 2020, findings from two well-known trials in the HIV clinical community—LATTE-2 and POLAR—were released by ViiV, the company developing Cabenuva. This research showed that after five years (256 weeks) of receiving Cabenuva, whether it was every two months or once monthly, people living with HIV had high, long-lasting rates of viral suppression while experiencing few side effects (which were generally tolerable).
Seeing data like this over a five-year span is not always common for drugs in development. It is reassuring that these research studies to test Cabenuva took the time to make sure the medication was effective over the long term, not just for a year or two.
How to Take Cabenuva
Cabenuva is FDA-approved in the United States to be taken once monthly as an intramuscular gluteal injection (i.e., in the buttocks). Since it is two separate medications in two separate vials, they are administered as two injections, one in each butt cheek—or both in the same one, but at least 2 centimeters apart.
When, Where, and Who Will Be Giving These Cabenuva Injections? (Can I Inject It Myself?)
Since this medication was studied as an injection in the buttock (gluteal) muscles, it is not recommended to inject the medication yourself. It is also not recommended to inject Cabenuva into the shoulder muscles, as we often do with other medications and vaccines.
(For folks who remember the injectable HIV medication Fuzeon (enfuvirtide, T-20) that was used for treatment-experienced people in the mid-2000s and could be self-administered, Cabenuva is a completely different story.)
For people who wish to start Cabenuva, the process will be as follows:
They’ll need to be undetectable on their current oral ART regimen.
They’ll take a 30-day lead-in dose of oral cabotegravir (30 mg daily) and oral rilpivirine (25 mg daily) before switching to the intramuscular injectable version.
After a month of oral therapy, they’ll receive what’s called a loading dose of injectable Cabenuva: 600 mg of intramuscular cabotegravir and 900 mg of intramuscular rilpivirine.
From month three onward, they’ll receive a maintenance dose of 400 mg intramuscular cabotegravir and 600 mg intramuscular rilpivirine every four weeks (give or take a week).
Since we are early in the process of rolling out Cabenuva, many of the details will have to be worked out by specific clinics and other medical locations that will be offering this injectable ART regimen.
What we do know is that, since Cabenuva must be refrigerated and then brought to room temperature before injection, the vials of medication will not be given to patients, so you won’t be able to carry your Cabenuva with you to a clinic or other health care facility. Instead, the drug must be held at the health care setting where the injection will be given, so coordination will have to happen between you and the clinic or doctor’s office when scheduling appointments.
That said, discussions are still ongoing about how providers and patients will handle this newly approved drug. Time will tell whether, for instance, the medication vials may be able to be stored at your local pharmacy, giving some people a little more flexibility in choosing where they receive their injections. For right now, however, Cabenuva will be stored at the location where you usually receive your HIV care and administered by a licensed medical professional.
What If I Miss an Injection of Cabenuva?
If you cannot make (or if you miss) a scheduled appointment for your injection, there is some flexibility in dosing: You can receive a Cabenuva injection up to seven days before or after the originally scheduled injection date. If you miss a planned injection by more than seven days, it is recommended that you instead take oral Vocabria (cabotegravir) and Edurant (rilpivirine) pills daily as a substitute until it’s time for your next injection, similar to the month of oral dosing “ramp up” or “lead in” you received before starting the injections.
How Much Does Cabenuva Cost in the U.S.?
The maker of Cabenuva, ViiV Healthcare, has said that the sticker price for the shots will be $5,940 for the initial loading dose and $3,960 per month afterward. These numbers are indeed scary, but there is a patient assistance program to help with any out-of-pocket costs, so speak with your medical provider and see if you qualify. Even if you have insurance, you could receive assistance to help with these costs and copays.
There is no generic version of Cabenuva, which may be a deterrent, depending on whether you have insurance and which insurance plan you have. Details are yet to come about how private insurers will be covering the cost of Cabenuva, and we also know little at the moment about Medicaid, Medicare, Ryan White, and the state-run AIDS Drug Assistance Program (ADAP).
Side Effects of Cabenuva
The potential side effects of Cabenuva are pretty much what one would expect from an intramuscular injectable ART regimen. The primary side effect reported has been injection-site reactions, usually mild to moderate (79% of the time) but occasionally severe (4% of the time). Yet only 1% of people getting those reactions stopped the medication because of it, and many reported that the pain at the injection site got better over time.
Other potential side effects of Cabenuva may include feeling feverish, fatigued, headachey, and experiencing musculoskeletal pain.
As with all HIV medications, it is important to remember that when you are starting a regimen for the first time, and sometimes when switching to a different regimen, the medications that slow down the HIV in your body may cause your immune system to get a much-needed boost. Within those first two weeks, many of these “side effects” may just be signs that your immune system is getting stronger.
If, however, after a couple of weeks, you are still having bothersome symptoms or they are progressing, let someone from your medical team know so that you can schedule a virtual or in-person meeting to discuss. Speak up, let your provider know, and discuss whether additional labs are needed or whether you may need to switch up your regimen altogether.
One note on pregnancy: At the time this article was written, there was not enough human data to assess whether there is any Cabenuva-related risk for individuals who are or may become pregnant, or any potential risk to a fetus.
Possible Interactions Between Cabenuva and Other Drugs
According to the drug label, it is recommended that the following drugs and herbs not be used when taking Cabenuva:
The anti-seizure drugs carbamazepine, oxcarbazepine, phenobarbital, and phenytoin.
The antibiotics rifabutin, rifampin, and rifapentine.
More than one dose of the steroid dexamethasone (oral or intravenous).
The herb St. John’s wort or its active ingredients, hypericin and hyperforin.
Although these medications and herbs may not cause side effects if you are also receiving Cabenuva injections, they may reduce the levels of Cabenuva in your body, making it less effective at slowing HIV down and keeping your viral load undetectable.
If you are planning to switch to Cabenuva and you’re taking medications for other conditions, make sure your medical provider knows about all of the medications you take. This can help safeguard against potential interactions. The website HIV Drug Interactions, maintained by the University of Liverpool, also has a helpful “interaction checker” where you can review potential interactions between medications you are taking.
Weighing the Pros and Cons of Cabenuva
Cabenuva has the potential to become a primary option for HIV treatment for many who prefer shots over daily pills.
It’s a powerful treatment for managing HIV via monthly injections.
There is little concern about kidney and bone issues that plague many oral HIV medication treatments.
It’s well tolerated and just as effective in maintaining an undetectable viral load as oral regimens.
It does not need any “booster” medications.
Not having to take daily pills.
It’s not approved as a first-line HIV treatment.
Injection-site reactions may be a problem for some.
It hasn’t been tested enough yet to comment on safety during pregnancy.
It will involve more frequent clinic visits than with oral HIV medication regimens.
It will not also be effective in treating people living with chronic, active hepatitis B.
What’s the Verdict on Cabenuva for HIV Treatment?
Cabenuva’s approval in the U.S. represents a watershed moment in HIV treatment: a long-acting, injectable regimen that gets rid of the need to take daily oral pills while still keeping people living with HIV undetectable. But while excitement over this new delivery system of ART is warranted, and it will undoubtedly be a great option for some, it may not be the best, or even a preferred, option for others.
Additionally, the studies demonstrating how effective Cabenuva was were in people living with HIV who were already virally suppressed on an oral ART regimen. We will need more information and additional studies before we recommend this in the future for people who are newly diagnosed and want to start with injectable therapy.
The medical community and HIV communities will also need time to assess logistical issues of cost, resources, access, patient assistance, and other considerations to make sure that every person who is eligible for or chooses this option for their HIV treatment regimen will be able to get it.
There is no doubt that this injectable ART regimen is safe and effective. We just have to make sure to set up and support social programs that can make this option available for everyone, so we can keep up with the science that got us here in the first place.
“Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study,”The Lancet. December 19, 2020. doi.org/10.1016/S0140-6736(20)32666-0