Cabenuva

Oral lead-in can be used to assess for safety and tolerability. The most common adverse reactions observed in 2% or more of people receiving Cabenuva in clinical trials were injection site reactions (83%, with 37% having at least Grade 2—moderate), 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 afterwards 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 (hepatotoxicity) 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. DHHS 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.

Cabenuva cannot be taken with carbamazepine, 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 (body mass index) 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 only complete HIV regimen that is injectable, is not approved for initial therapy or for individuals whose viral load is not suppressed, although studies are being conducted to look at safety and effectiveness in this setting. In persons with suppressed virus, no hepatitis B, and no resistance to its components, Cabenuva can be given by injections every one or two months (with a higher dose for bimonthly administration.) Balancing out the convenience of dosing every two months is the slightly higher incidence of drug resistance seen in clinical trials of the bimonthly regimen. Initially, Cabenuva required “lead in” dosing with oral cabotegravir and rilpivirine for a month before beginning the injectable regimen, but one study found that omitting the oral lead in and starting “direct to inject” is safe and effective. This is now an FDA-approved dosing option. If doses must be missed, a bridging oral regimen should be used. ViiV provides the oral lead-in and bridging regimens to Cabenuva users at no additional cost. There are insufficient data to recommend starting Cabenuva during pregnancy, and persons who are pregnant and choose to continue Cabenuva should be monitored more closely to ensure viral suppression. 

Injection site reactions are the most common side effect 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 1.5kg (about 3.3 lbs) by 48 weeks.  

Cabenuva has some important drug interactions. Many common medicines for seizures and tuberculosis, and 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. 

If you are interested in Cabenuva, it is important to consider whether you would be able to routinely get to clinic appointments every one or two months, which is probably more frequently than you now go for HIV monitoring for your oral regimen. At present, injections cannot be self-administered. Levels of the drugs may persist in the body a year or longer, 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 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.  

A common issue with Cabenuva is simply getting it covered by insurance. The cost is very high, at a wholesale acquisition cost of $6,088 for the loading initial dose and for bimonthly maintenance doses, and $4,059 for monthly maintenance doses. This 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 called in at the pharmacy) or as a medical benefit (like a flu shot that you get at your clinician’s office.) ViiV has a patient assistance program that aims to pick up enough of your out-of-pocket drug cost to make Cabenuva feasible (while allowing them to keep prices high), but many patients and clinicians continue to struggle with access. Insurance denial has been a real 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 simply 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. Injections allow us to get on with our lives, and not be weighed down with the daily burden of taking pills. 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. If you want it, demand it—it’s your choice. Some studies suggest the vast majority of those who got on an injectable will never go back to taking pills. I could go on about provider bias, but you get the point: get what you need to make your life work for you!