By: Sharon Joseph PharmD Candidate c/o 2022 and Salma Hewady, PharmD
Human immunodeficiency virus (HIV) is a single-stranded retrovirus that attacks the immune system, predisposing the host to opportunistic infections and malignancies. If not properly treated, HIV can progress to Acquired Immunodeficiency Syndrome (AIDS). Goals of therapy include restoration of immune function, suppression of HIV viral load, prolonged survival, and transmission prevention.¹ Most preferred HIV-1 treatment regimens entail the use of daily oral antiretroviral (ARV) medications. The mainstay of current treatment consists of two nucleoside reverse transcriptase inhibitors (NRTIs) combined with a third ARV medication from one of the following drug classes: a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase strand transfer inhibitor (INSTI).²
Adherence to ARV therapy is imperative for successful management of HIV. Interruption of therapy can result in virologic failure, drug resistance, elevated healthcare costs, and increased morbidity/mortality.³ Simplification of ARV regimens with the emergence of combination medications promotes long-term medication adherence, reduces risk of treatment failure, and improves quality of life.⁴ Approved by the Food and Drug Administration (FDA) in January 2021, cabotegravir/rilpivirine (Cabenuva®) is the first extended-release injectable indicated for the treatment of HIV-1. This promising new ARV regimen consists of an INSTI (cabotegravir) and an NNRTI (rilpivirine), and is intended to replace current therapy in adult patients who are virologically suppressed (HIV-1 RNA < 50 copies/mL) with no history of treatment failure/resistance to either component of the combination drug.⁵
Prior to the initiation of cabotegravir/rilpivirine injections, patients must take a trial regimen of oral cabotegravir 30mg and rilpivirine 25 mg tablets once daily for one month (at least 28 days) to assess tolerability. This is referred to in the package insert as the “Oral Lead-in” period. After this oral-lead in period, patients will take the “initiation” injections which consist of long-acting cabotegravir (600mg/3mL) and rilpivirine (900mg/3mL). These injections must be administered by a healthcare provider in separate gluteal sites either on opposite sides or 2cm apart. For the third month and beyond, patients will be given the continuation doses of the 2 injections which consist of cabotegravir 400 mg (2mL) and rilpivirine 600mg (2mL).5,6
Important for patients and clinicians to consider are the unique missed dose instructions for cabotegravir/rilpivirine. As always, patients should be strongly encouraged to take their medications as prescribed. In the event that a patient misses their dose of medication, there are specific sets of instructions outlined in the package insert. There are two categories: “planned missed injections” and “unplanned missed injections”. If a patient plans to miss a scheduled injection visit by >7 days, they are instructed to administer oral therapy to replace up to 2 consecutive monthly injections. The first dose of oral therapy should be administered at least 1 month after the last injections, and continued until the day the injection dosing is restarted. If monthly injections are unintentionally missed or delayed by >7 days and oral therapy has not been administered in the interim, patients should be clinically reassessed to determine appropriateness of resuming injection dosing. If injection dosing will be continued, administer as follows: continue with cabotegravir 400 mg and rilpivirine 600 mg IM monthly injections if it has been less than or equal to 2 months since the last injection. If it has been greater than 2 months, reinitiate with cabotegravir 600 mg and rilpivirine 900 mg IM injections, then continue to follow the cabotegravir 400 mg and rilpivirine 600 mg IM monthly injection dosing schedule.⁵
Adverse reactions for cabotegravir/rilpivirine mainly consisted of injection site reactions, fatigue, sleep disorders, and dizziness. Aside from hypersensitivity reactions to the medication, precautions included hepatotoxicity (for which liver function tests should be monitored and the medication discontinued if hepatoxicity is suspected), and depressive disorders (for which medication evaluation is warranted). Cabotegravir/rilpivirine should not be co-administered with UGT1A1 inducers (for example, phenobarbital and rifampicin) or CYP 3A4 inducers (for example, clarithromycin, erythromycin, ketoconazole, diltiazem, verapamil). The reasoning is that these medications will reduce the serum concentration of cabotegravir/rilpivirine , which will lead to suboptimal patient outcomes. Furthermore, because this medication is considered a complete HIV therapy regimen, it should not be administered concomitantly with other antiretroviral therapies.⁵
It is important to note that although the injectable dosage form of cabotegravir/rilpivirine may be considered by some to be inconveniencing, its monthly dosing frequency provides therapy simplification, a huge advantage for patients with a history of non-adherence. Injections must be administered by a healthcare provider, therefore patients with poor follow-up may not be ideal candidates for therapy. Given the novelty of cabotegravir/rilpivirine, conventional ART may also be more cost-effective for uninsured patients.
In conclusion, cabotegravir/rilpivirine is a novel form of therapy that has the potential to impact the lives of many patients living with HIV-1 who struggle with nonadherence. There are advantages and disadvantages which should be taken into consideration, as previously discussed. Ultimately, the decision to initiate cabotegravir/rilpivirine should be a shared decision making process between the patient and the healthcare provider. Pharmacists, as the most accessible healthcare providers, play an essential role in the delivery of healthcare, and should be cognizant of such drug updates when they occur.
- CDC. About HIV. cdc.gov. https://www.cdc.gov/hiv/basics/whatishiv.html. Last reviewed June 1st 2021.
- Clinical info 1:“Backbone”. Backbone | NIH, clinicalinfo.hiv.gov/en/glossary/backbone.
- Nachega JB, Marconi VC, van Zyl GU, et al. HIV treatment adherence, drug resistance, virologic failure: evolving concepts. Infect Disord Drug Targets. 2011;11(2):167-174. doi:10.2174/187152611795589663.
- Clinical info 2: “Regimen Simplifications”. Regimen Simplification | NIH, clinicalinfo.hiv.gov/en/glossary/regimen-simplification
- Cabenuva (cabotegravir rilpivirine) [package insert]. Research Triangle Park, NC; Viiv Healthcare; Revised 01/31/2021.
- Viiv Healthcare. Cabenuva. cabenuvahcp. https://cabenuvahcp.com/. Published 01/31/2021