cabotegravir/rilpivirine long-acting (CAB LA/RPV LA)
Standard DoseTwo long-acting intramuscular gluteal (butt muscle) injections once monthly. Consists of one injection of long-acting cabotegravir (an INSTI) and one injection of long-acting rilpivirine (a NNRTI). No food restrictions.
For adults switching from a stable HIV regimen who have undetectable viral load (less than 50 copies per mL) with no history of antiretroviral treatment failure and no drug resistance or suspected resistance to cabotegravir or rilpivirine. A month of daily oral lead-in therapy is required before injections begin, consisting of a 30 mg tablet of cabotegravir (Vocabria) and a 25 mg tablet of rilpivirine (Edurant). Oral rilpivirine must be taken with food; the injectable does not. If up to eight weeks of treatment is missed (four injections total), restart therapy with the maintenance dose of 400 mg CAB LA plus 600 mg RPV LA. If more than eight weeks of therapy has been missed, restart treatment with the higher initial dose of 600 mg CAB LA plus 900 mg RPV LA, then continue with the lower doses thereafter. The oral medications can also be used as “bridging” if shots cannot be obtained on time. Initiate injections on last day of oral lead-in. Increased monitoring is recommended when CrCl is less than 30. The effect of severe liver impairment on Cabenuva is unknown.
See Edurant; Vocabria is not available separately
See package insert for more complete information on potential side effects and interactions.
AWP28-day oral lead-in provided at no cost Loading dose (600 mg/900 mg):
Maintenance dose (400 mg/600 mg):
$4,752 (estimated) per month
Potential Side Effects and Toxicity
Oral lead-in should be used to assess for 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 (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) intra- venous administration and began to resolve with- in a few minutes after injection in clinical studies: difficulty breathing (dyspnea), abdominal cramp- ing, 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. Liver toxicity (hepatotoxicity) has been reported with or without pre-existing liver disease or risk factors. People with underlying live 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 patients with pre-existing psychiatric conditions on an INSTI. Serious or severe hypersensitivity reactions have occurred with other INSTIs and could occur with Cabenuva. Monitor for signs of hypersensitivity, including elevated liver transaminases, and treat as needed. New data associate INSTIs with weight gain; see a different INSTI page for more information. There was a median weight gain of 3.3 pounds in Cabenuva trials.
Potential Drug Interactions
New interactions may be discovered after approval. 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. 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.
As ViiV Healthcare pointed out, Cabenuva changes HIV treatment from 365 dosing days per year to just 12. FDA approval was based on two Phase 3 studies, ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen). Residual concentrations of cabotegravir and rilpivirine may remain in the body for more than a year after discontinuation, but are not expected to affect the use of subsequent HIV drugs.
Dr. Ross Slotten says (from 2020 HIV Drug Guide):
Cabenuva [likely name once FDA approved] is composed of the new integrase strand transfer inhibitor (INSTI) cabotegravir manufactured by GlaxoSmithKline and Janssen’s NNRTI rilpivirine (Edurant). What’s novel about this combination is that it is given as a once-monthly injection in the muscle (ouch!). Moreover, like Juluca, Cabenuva doesn’t contain any NRTIs. In two Phase 3 studies, known as ATLAS and FLAIR, Cabenuva’s efficacy matched that of Triumeq and other three-drug regimens. Patients selected for the studies had to be virally suppressed for at least six months and have no prior history of treatment failure to any regimen. Local injection site reactions were said to be mild and didn’t lead to discontinuation of the medication in study subjects. In fact, the medication was otherwise very well tolerated. Presumably, Cabenuva will not be prescribed as a first-line regimen, at least initially. Patients would be switched to Cabenuva after achieving and maintaining undetectability with another anti-HIV regimen. Still, I have questions. Despite its relative convenience, will people with HIV be willing to switch to an injectable therapy? How long a grace period do they have if they don’t return for treatment in 4 weeks? ViiV, the division of GSK that will be marketing Cabenuva, recently filed for FDA approval, but the FDA rejected the application not because of safety or efficacy concerns but because of incomplete information about quality control issues related to storage, distribution, and packaging information. Presumably, further investigation and clarification will lead to eventual FDA approval. Whether Cabenuva will surpass Biktarvy or Triumeq in the race to Olympus remains unclear.
Activist Bridgette Picou says (from 2020 HIV Drug Guide):
This two-drug regimen will soon be an exciting new option in drug therapy. The once- or twice-monthly injectable dosing offers a freedom from taking medication daily and feeling tied to your regimen, although keep in mind that it requires a commitment to scheduling. If you are a person who splits time living between different cities seasonally, or who travels a lot, you will want to make sure you have a network in place, and that the medication is available and covered in those places. This is a deep intramuscular injection, which means it needs to be given in a doctor’s office. Your tolerance for injections is also a consideration. The most common reported side effect is injection site pain, which is temporary. Even with all that, for people with adherence issues, or those who want to keep their medication routine private, this will be a fantastic alternative.