CAB LA/RPV LA
Standard DoseClinical trials of this investigational regimen used a long-acting cabotegravir injection of 400 mg plus 600 mg long-acting rilpivirine injection every month. There was a month-long oral lead-in using 30 mg cabotegravir plus 25 mg rilpivirine prior to initiating injections. Oral medication is also expected to be used as “bridging” if shots cannot be obtained on time. The cabotegravir tablet may not otherwise be available on the market. This regimen consists of the NNRTI rilpivirine with the new INSTI cabotegravir. Oral rilpivirine must be taken with food; the injectable does not need to be taken with food. After the month-long oral lead-in, two loading doses are administered consisting of two 3 mL injections of cabotegravir plus rilpivirine. Maintenance dose consists of two 2 mL injections of cabotegravir plus rilpivirine monthly.
See Edurant; cabotegravir is not yet available
See package insert when available for more complete information on potential side effects and interactions.
AWPNot yet established.
Potential Side Effects and Toxicity
In one study, injection site reactions with mild, short-term (two to five days) redness, pain, and swelling was reported in 84% of all injections. Moderate symptoms were reported in 15% of injections. Less than 1% of patients discontinued the study due to injection site reactions. There have been rare reports of depression and suicidal ideation, primarily in patients with a history of psychiatric illnesses, in people receiving INSTI-based regimens. The DHHS guidelines recommend closely monitoring patients with pre-existing psychiatric conditions on an INSTI.
Potential Drug Interactions
New interactions continue to be discovered after drug approval (cabotegravir is the new medication). Not intended to be taken with other HIV medications, unless prescribed that way. If used with abacavir/lamivudine during the initial oral induction phase, as this regimen was also studied, be aware of possible drug interactions with these agents (see Epzicom page). During the initial oral induction phase with rilpivirine, it is not recommended to co-administer carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, proton pump inhibitors (Aciphex, Dexilant, Nexium, Prevacid, Prilosec, Protonix), or St. John’s wort. Antacids should be taken two hours before or at least four hours after oral Edurant. Acid-reducing drugs (Pepcid, Tagamet, Zantac, and Axid) should be taken 12 hours before or 4 hours after an oral Edurant dose. Some of these interactions will no longer be relevant once injection therapy begins; however, see package insert when available for guidance. See Edurant page for more interactions. 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.
There was surprise and disappointment when the FDA didn’t grant approval to this drug in December 2019. Instead the FDA sent ViiV Healthcare a “complete response letter.” ViiV reported that the FDA referred to “Chemistry Manufacturing and Controls,” and that there were no safety issues raised by the FDA. The company said it will work with the FDA on the drug’s approval. ViiV had a factory built specifically for the production of this medication, that’s how different it is. In fact, this page represents a brand new category for the drug guide—a long-acting complete regimen for HIV treatment. This antiretroviral regimen is taken once a month, as two intramuscular injections. That’s it. Or as ViiV Healthcare pointed out, it changes HIV treatment from 365 dosing days per year to just 12. People who are adherent to their HIV regimen now may be eligible to switch to this med when approved. The trade-off with long-acting treatment is the requirement for near-perfect adherence and visiting your doctor’s office 12 times a year instead of two or three. The treatment is also one injection per butt muscle. Cabotegravir is from the top-of-the-line HIV medications right now, the INSTI drug class. They have great efficacy and are, in general, easy to take. Rilpivirine is already on the market in a variety of oral formulations (Complera, Edurant, Juluca, and Odefsey). Rilpivirine is not available separately as an injectable. Cabotegravir-LA is also being studied for HIV prevention or PrEP using one 3 mL intramuscular injection in the gluteal area every two months. The lead-in oral dosing is used to establish the safety and tolerability of cabotegravir prior to long-acting injection. For example, if an allergic reaction occurs, it can be out of the system in a day or two. In the LATTE-2 study with people on first-time HIV therapy, cabotegravir plus rilpivirine given every 4 weeks or every 8 weeks was found to be as effective as the traditional three-med (even if only as one pill) oral combination given to people in the control group of the trial. There was some virologic failure in the 8 week group vs. none in the 4 week; hence, research went forward with only 4 week dosing. This success was out to 96 weeks (nearly two years). Moreover, the majority of participants given shots in the Phase III ATLAS study (more than 96%) said they preferred the injections every month or two months to taking their previous daily HIV oral regimen, despite any side effect or injection site reaction.
Dr. Ross Slotten says:
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:
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.