Cabenuva

Oral lead-in can be used to assess for safety and tolerability, especially in individuals who have a history of rash, allergies or severe intolerances to past ART medications. The most common adverse reactions observed in 2% or more of people receiving Cabenuva in clinical trials were injection site reactions, fever, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Serious post-injection reactions reported within minutes of administration (in less than 1% of people injected) may have been associated with inadvertent (partial) intravenous administration and began to resolve within a few minutes after injection in clinical studies: difficulty breathing, abdominal cramping, agitation, flushing, sweating, oral numbness, and changes in blood pressure. People should be observed for approximately 10 minutes after injections to monitor for potential reactions. Individuals with injection pain can use an ice pack or heating pack and are advised to stretch and remain active. It is strongly discouraged to massage the area.

Liver toxicity has been reported with or without pre-existing liver disease or risk factors. People with underlying liver disease or marked elevations in transaminases may be at increased risk for rising transaminase level or worsening of current elevated levels. Monitor for signs of hypersensitivity. HHS guidelines recommend closely monitoring people with pre-existing psychiatric conditions on an INSTI. Data associate INSTIs with weight gain. There was a median weight gain of 3.3 pounds in Cabenuva trials.  People with buttock implants or fillers may not be good candidates for this medication due to concerns about drug absorption.

Cabenuva cannot be taken with carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (more than one dose), or St. John’s wort. Clinical monitoring of methadone is recommended because it may need to be adjusted in some people due to decreased levels. Macrolide antibiotics like azithromycin, clarithromycin, and erythromycin are expected to increase concentrations of rilpivirine and are associated with a risk of QT prolongation (these abnormal heart rhythms can make the heart stop) or possible torsade de pointes. Other medications that may increase the risk of QT prolongation when taken with Cabenuva, such as levofloxacin, moxifloxacin, aripiprazole, escitalopram, fluoxetine, donepezil and ondansetron, should be used with caution.

Where possible, consider alternatives such as azithromycin, which increases rilpivirine concentrations less than other macrolides. Antacids should be taken at least 2 hours before or 4 hours after oral cabotegravir and oral rilpivirine, but do not interact with injections. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions which are not listed here.

Residual concentrations may remain in the body for more than a year after discontinuation. Therefore, it is essential to initiate an alternative, fully suppressive regimen no later than one month after the final injection doses of Cabenuva. If virologic failure is suspected, switch to an alternative regimen as soon as possible. Analyses indicate that having two of the following baseline factors may be associated with an increased risk of virologic failure: archived rilpivirine resistance mutations, HIV-1 subtypes A6/A1 or BMI greater than 30 kg/m2. People with a history of exposure to an NNRTI may consider obtaining a GenoSure Archive resistance test to assess archived mutations that may decrease the susceptibility to rilpivirine. Pregnant people should talk with their provider about opting for more frequent viral load testing or switching to a preferred or alternative 3-drug regimen recommended in pregnancy. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider;

GO TO apregistry.com.

Dr. Melanie Thompson:

Cabenuva, the first completely injectable regimen for HIV treatment, is not FDA-approved for initial therapy, but is approved for people whose virus is suppressed (HIV-1 RNA less than 50 copies/mL) on stable ART and who have no history of treatment failure and no known or suspected resistance to cabotegravir or rilpivirine. Because Cabenuva does not contain medications active against hepatitis B (HBV), people with HBV will need to take additional oral HBV treatment and screening for HBV is essential before starting Cabenuva. Cabenuva can be given monthly or, at higher doses, every two months after two loading doses given one month apart. While oral cabotegravir and rilpivirine are available as a “lead in” for a month, the FDA also has endorsed a “direct-to-inject” method, which decreases the risk of non-adherence to oral meds. Cabenuva should not be initiated in pregnancy due to insufficient data and concern about rilpivirine levels during pregnancy, since low levels of oral rilpivirine have been observed during pregnancy. If you are pregnant and choose to stay on Cabenuva, viral load should be monitored carefully.

Balancing out the convenience of dosing every two months is the slightly higher incidence of drug resistance seen in clinical trials using the bimonthly regimen. It is important to consider whether you would be able to routinely get to clinic appointments every one or two months, which may be more often than your current schedule for HIV monitoring. Injections cannot be self-administered. Levels of the drugs may persist in the body for more than a year, but when levels drop below the concentration needed to suppress virus, viral resistance to one or both drugs can result, so it is important to attend visits exactly as scheduled. If you know you are going to miss a visit by more than a week, tell your HIV clinician so you can “bridge” with oral medicines to keep your virus suppressed and prevent viral resistance. If you are on Cabenuva and you decide that injections are not for you, tell your clinician right away so you can start oral treatment again at the appropriate time to keep your virus suppressed. Longer needles (2 inch) should be used for people with BMI above 30 kg/m² to ensure that the injection is into muscle rather than fat.

Although Cabenuva is not FDA-approved for individuals whose virus is not suppressed, studies are being conducted to look at its safety and effectiveness for people who have repeatedly struggled with adherence to oral therapy. The LATITUDE study showed that monthly injections of Cabenuva were superior to continuing oral treatment in people who have struggled with oral therapy, but in this study most participants achieved viral suppression prior to switching to Cabenuva. Recently, the IAS-USA amended its guidelines to recommend Cabenuva for a narrowly defined group of people whose virus is not suppressed due to inability to take oral therapy consistently, and who are at high risk for disease progression or death. This group is defined as being unable to take oral therapy successfully in spite of extensive efforts and clinical support; having CD4 counts below 200/µL or a history of an AIDS-defining condition; and having virus that is sensitive to both cabotegravir and rilpivirine. The purpose of this recommendation is to balance the risk of virologic failure with the high risk of death in people with severe immune suppression and limited options. It should be emphasized that this regimen should not be used for people whose virus is not suppressed but whose CD4 counts are good and who have other options. For these persons, every effort should be made to suppress the virus before transitioning to Cabenuva. 

Injection site reactions are the most common Cabenuva side effects but are generally mild and resolve quickly. The most common non-injection side effects (occurring in at least 4% of people in the FLAIR and ATLAS trials) were fever, fatigue and headache. Sleep disorders and rash occurred in about 2% of participants. Persons receiving Cabenuva in the FLAIR and ATLAS studies gained about 1.5 kg (about 3.3 lbs) by 48 weeks. 

Cabenuva has some important drug interactions. Many common medicines for seizures and tuberculosis as well as St. John’s wort are contraindicated, as is dexamethasone when given in more than a single dose. While azithromycin does have a potential interaction with rilpivirine, it can be used with caution when absolutely required but its cousins, clarithromycin and erythromycin, should be avoided. Methadone maintenance doses may need to be adjusted and should be monitored. While acid-blockers lower oral rilpivirine levels, they do not affect injectable rilpivirine. 

A common issue with Cabenuva is simply getting it covered by insurance. The cost is very high and does not include administration charges or office visits. Reimbursement is confusing, and may depend on whether the drug is handled as a pharmacy benefit (like an oral medicine that is ordered through a pharmacy) or as a medical benefit (like a flu shot that you get at your clinician’s office). ViiV has a patient assistance program for people with commercial insurance, covering up to $13,000 of out-of-pocket costs. The program aims to pick up enough of your out-of-pocket drug cost to make Cabenuva feasible (while allowing ViiV to maintain its price) but it does not apply to people with government insurance such as Medicare/Medicaid. Many patients and clinicians continue to struggle with access. Insurance denial has been an obstacle for many patients who might benefit from this regimen, and the burden of arguing with insurance companies is a huge downside for clinicians who are trying to provide access to the regimen.

Activist Joey Wynn:

The great divide: Providers don’t like it, in stark contrast to many people who want to move to injectables. Do you have an “on the go” lifestyle? Travel a lot for work? There are lots of other reasons to not want a bottle of HIV medication in your home. Pill fatigue? Is that bottle a reminder of your condition? Although definitely not for everyone, this is the next phase of evolution in HIV therapy. You can usually see extreme bias with many providers because this disrupts their existing clinic flow, and they give you 10 lame reasons why not to evaluate this option. Some studies suggest the vast majority of people who got on an injectable will never go back to taking pills. I’ve spoken at length with nearly 100 people in Florida who are on it, and none of them will go back to taking pills again. Understandably, there are issues of access for people on private insurance, clinic flow and limited distribution shortages meaning advocates need to demand improved pipeline delivery from the manufacturer so people can get what they need, want and require with fewer difficulties.