Cabenuva

Oral lead-in should 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), pyrexia, 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 (dyspnea), abdominal cramping, agitation, flushing, sweating, oral numbness, and changes in blood pressure. Instructions for injection should be followed carefully to avoid accidental intravenous administration. People given injections should be observed for approximately 10 minutes afterwards to monitor for potential reactions. Individuals with pain from injections 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 (a lab measure that indicates there is damage to the liver) may be at increased risk for rising transaminase level or worsening of current elevated levels. Depressive disorders (including depression, major depression, depressed moods, altered moods, mood swings, dysphoria, negative thoughts, or suicidal ideation and attempts) have been reported with Cabenuva. People experiencing depressive symptoms should be monitored. DHHS guidelines recommend closely monitoring people with pre-existing psychiatric conditions on an INSTI. Monitor for signs of hypersensitivity, including elevated liver transaminases, and treat as needed. Data associate INSTIs with weight gain. There was a median weight gain of 3.3 pounds in Cabenuva trials.

Cabenuva is contraindicated with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (more than one dose), or the herb 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. Where possible, consider alternatives such as azithromycin, which increases rilpivirine concentrations less than other macrolides. See Edurant for oral lead-in. 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, prescribe 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 individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; go to apregistry.com.

Dr. Melanie Thompson:

Cabenuva is the first complete injectable regimen for HIV treatment and can be given once once every two months. People who hate pills, or are just sick of taking them, and don’t mind injections might be very interested in this regimen, but it’s not for everyone. Injection site reactions are the most common side effect but are generally mild and resolve quickly.

The FLAIR study included 111 people who switched from oral DTG/ABC/3TC directly to injectable CAB + RPV at week 100 with similar safety and efficacy 24 weeks later. This suggests that a direct-to-injection strategy should be explored in clinical trials. 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.

If you are interested in Cabenuva, it is important to consider whether you would be able to get to clinic appointments every month or every two months. Levels of the drugs may persist in the body a long time (up to a year or longer), but when they drop below the levels 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 are on Cabenuva and you decide that injections are not for you, tell your HIV care provider right away so you can start oral treatment again at the appropriate time to keep your virus suppressed.

The cost of Cabenuva is extremely high, at a wholesale acquisition cost of $5,940 for the loading initial dose and $3,960 for monthly maintenance doses. This does not include what your care provider’s office charges for administering the drugs, or for office time. Of course, ViiV has a patient assistance program that aims to pick up enough of your out-of-pocket drug cost to make Cabenuva feasible while keeping prices very high, but it is really unfortunate that prices remain at this egregious level.

Activist Michael Broder:

According to surveys most people taking Cabenuva like it, and would not want to go back to daily pills.