DISCLAIMER: This article is provided as commentary and discussion, not direct medical advice. Before making any medical decision, consult with your medical provider.
Since zidovudine was approved in the 1980s, Human Immunodeficiency Virus (HIV) treatment has largely consisted of daily oral medications – and there are many. As Dr. Rebecca Lamore explored in a previous Pharmacist Consult article, more therapies for HIV are in the pipeline.
This year, a new medication for treating HIV was approved by the Food and Drug Administration (FDA): Cabenuva® (cabotegravir/rilpivirine). Cabenuva® consists of injecting two long-acting medications into the muscle which would eliminate the need for patients to take daily medication. The burden of eliminating the need for daily medication is appealing, but like with most things, there is more than meets the eye.
The devil is in the details, so this discussion will dive into this newly-approved product and discuss its implications for providers and patients alike.
Overview
Cabenuva® consists of two drugs formulated as separate extended-release injections: cabotegravir, an integrase inhibitor (INSTI), and rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI). INSTIs and NNRTIs are two classes of medications commonly used to treat HIV – these two drugs can work together to suppress the amount of HIV in the body.
Cabenuva® is currently approved for patients who are already taking medication and are virologically suppressed (Table 1). It is intended as a replacement for a patient’s current oral HIV medications, not for patients who are newly diagnosed and have not started treatment.
Table 1. FDA-Approved Indications for Cabenuva®
| Indication |
| Complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are: Virologically suppressed (HIV-1 RNA < 50 copies/mL) On a stable antiretroviral regimen No history of treatment failure No known/suspected HIV resistance to either component |
| Contraindications |
| Previous hypersensitivity reaction to either component of Cabenuva® Simultaneous use with other medications: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin Rifampin, rifabutin, rifapentine Dexamethasone (> 1 dose) St. John’s wort |
Unfortunately, patients will not be able to immediately switch from their oral medications to injections. Because Cabenuva® is a long-acting injection, a month-long trial of the two drugs as oral formulations is required to assess for tolerability and safety.
To start using Cabenuva®, the following steps are typically followed:
- Vocabria® (cabotegravir) 30 mg by mouth daily with food + Edurant® (rilpivirine) 25 mg by mouth daily with food for at least 28 days
- On the last day of oral medications, the patient will receive two 3 mL loading dose injections into the gluteal muscle of cabotegravir 600 mg and rilpivirine 900 mg
- Every 4 weeks +/- 7 days, the patient will receive two 2 mL maintenance dose injections into the gluteal muscle of cabotegravir 400 mg and rilpivirine 600 mg
Not surprisingly, the most commonly reported adverse reaction to Cabenuva® in clinical trials was injection site reactions, which occurred in 83% of patients. Pain was the most commonly reported injection site reaction followed by nodules (lumps beneath the skin, 12%), indurations (tissue hardening, 10%), and swelling (7%). These reactions lasted for about 3 days and after 1 week most patients had their reactions resolve. Only 1% of patients in the clinical trials for Cabenuva® stopped treatment due to injection site pain.
Other adverse reactions included pyrexia (fever) which occurred in 8% of patients, and reactions common to other HIV medications: fatigue (5%), headache (4%), and nausea (3%).
Table 2. Managing Missed Injections
| Planned Missed Injection by More Than 7 Days | Take oral components (same dose as lead-in period) for up to 2 consecutive missed visits |
| Unplanned Missed Injections Without Oral Therapy | Less than 2 months since last injection: 400 mg/600 mg (maintenance dose) More than 2 months since last injection: 600 mg/900 mg (loading dose) |
Obtaining Cabenuva®
Getting Cabenuva® will not be like the typical trip to the pharmacy.
Some patients may be familiar with getting medications from their physician’s office (samples, some injections, etc.), however most are used to going to a pharmacy. Unlike other medications that a physician may have in their office, this is a medication that is ordered directly from the manufacturer on a patient-by-patient basis.
Here’s what that process looks like:
- The healthcare clinic will submit an order to the manufacturer of Cabenuva®, ViiV Healthcare, through viivconnect.com along with the patient’s insurance information (if applicable). This acts as the prescription. This is the only way to get Cabenuva®.
- The manufacturer (or a specialty pharmacy contracted with the manufacturer) will then send two medications for the oral lead-in period, Vocabria® (cabotegravir) and Edurant® (rilpivirine), to the clinic.
- The manufacturer will then send the Cabenuva® loading dose kit to the clinic.
- On the last day of the oral lead-in period, the patient will come to the clinic to receive their injections.
The manufacturer helps simplify the process by supplying both drugs for the oral lead-in period. However, they will not always do this for patients who need the oral medications.
If patients are going to miss an injection and be “bridged” with oral medications, they will actually get their medications from two different places. Vocabria® will come from the clinic and is supplied by the manufacturer. Edurant® will need a prescription to be filled at a pharmacy. This is likely due to the fact that ViiV Healthcare owns Vocabria® but another company own Edurant®. Unfortunately, patients cannot make a single stop for the oral medications as Vocabria® will not be supplied to pharmacies.
Catch-22
The initial excitement around Cabenuva® revolved around how this would be useful in helping patients who are non-adherent to their HIV treatment stay virologically suppressed. Similarly to how long-acting injections of antipsychotics are useful for patients with schizophrenia who “fail” oral medication, a long-acting injection for HIV would be a game-changer for patients with detectable HIV viral loads who have “failed” oral medication.
But, as shown in the FDA-approved indication, Cabenuva® is not approved for patients with detectable viral loads. The studies of Cabenuva® were not conducted in patients with unsuppressed HIV. Patients in the studies were given conventional oral HIV regimens and obtained an undetectable viral load result prior to switching to Cabenuva®. Patients who are non-adherent to daily oral medications for treatment of their HIV are likely the same patients with detectable viral loads and also more likely to have a history of virologic failure. The patients who would receive the most benefit from a long-acting HIV treatment are the same patients that are currently not indicated for Cabenuva®.
Conclusion
Cabenuva® is a promising step forward for improving the quality of life for patients living with HIV. If the FDA approves Cabenuva® to be used every 2 months based upon data from the ATLAS-2M study, then the utility of Cabenuva® would be greatly improved.
Ideally, this long-acting injection would be indicated for patients with detectable viral loads due to non-adherence to oral medications; however, that is not the current state of things. Hopefully, future data will become available to support the use of long-acting injections such as Cabenuva® for these patients.
Using the drug is not as simple as it may appear. Navigating the process of obtaining the medications and managing missed doses can be complex and can generate more questions than answers. It is imperative that patients be given a thorough walkthrough of the intricacies of this product prior to starting it.
Newer 1st generation products often have kinks to iron out. The path has been blazed for future long acting injections to treat HIV. For now, Cabenuva® will likely be used by patients who are already successful in managing HIV. These patients are probably highly motivated patients who are adherent to current oral medication regimens. In the future, let’s hope that the indication expands to those patients who would benefit most.
References:
- FDA-Approved HIV Medicines. HIVinfo.NIH.gov. Last updated 8 February 2020. Accessed 15 May 2021. Accessible via: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/fda-approved-hiv-medicines
- Lamore R. What’s Next? A Look at the Future of HIV Treatment and Prevention. Pharmacist Consult. Published 29 March 2021. Accessed 15 May 2021. https://www.pharmacistconsult.com/whats-next-a-look-at-the-future-of-hiv-treatment-and-prevention/
- Cabenuva [prescribing information]. ViiV Healthcare; 2021. Accessed 13 May 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212888s000lbl.pdf
Resources for download:
- NASTAD, HIVMA, American Academy of HIV Medicine Fact Sheet (February 2021)
- NIH HIV Guidelines on treatment with long-acting injections
About The Author
