Introduction

HIV and AIDS are trending health care topics. As more patients get tested and gain access to HIV medications, rates of infection and progression to AIDS decrease and survival rates increase. One of the limiting factors within HIV treatment, however, is patient adherence. Many HIV regimens require patients to take multiple doses of medications per day. If patients do not adequately adhere to the medication regimen, they will be unable to reduce viral load to an undetectable level. Because of evidence of poor adherence in people receiving treatment for HIV and AIDS, finding ways to improve adherence is critical.¹ In January 2021, the FDA granted approval for the use of a new medication that could potentially address this issue: Cabenuva (cabotegravir and rilpivirine, approved for the treatment of HIV-1 infection).

Pharmacology

Cabenuva is the first combination injectable product approved for adults with HIV-1 infection and is a co-packaging of cabotegravir and rilpivirine extended-release injectable suspensions. Cabotegravir is a novel integrase strand transfer inhibitor, whereas rilpivirine is a nonnucleoside reverse transcriptase inhibitor that has been used as an oral agent in antiretroviral therapy (ART) regimens since 2011.² These agents have different mechanisms of action but work together to prevent replication of HIV in the body, decreasing viral load over time. Oral cabotegravir (Vocabria) was also approved because of the need for oral lead-in dosing before beginning intramuscular injection.³ Rilpivirine is approved for the treatment of HIV and is used in other combination agents as well.⁴

Dosing Information

Cabenuva use should be preceded by daily doses of both cabotegravir 30-mg and rilpivirine 25-mg tablets for at least 28 days. After lead-in therapy, initial injections of Cabenuva should be administered using the 600/900-mg kit, which is given as gluteal intramuscular injections of each product (cabotegravir 600 mg and rilpivirine 900 mg) at the same visit.⁵ One month after the initial injections, Cabenuva 400/600 mg can be given as two separate gluteal intramuscular injections (cabotegravir 400 mg and rilpivirine 600 mg) at the same visit. Subsequent doses of Cabenuva 400/600 mg should be given monthly (±7 days).⁵ Missed doses may be supplemented with oral cabotegravir therapy for up to 2 months, and patients may restart therapy at a normal injection dose as long as the missed dose interval is 2 months or less. If the patient is beyond the 2-month period, reinitiation at the higher starting dose is required.⁵

Safety Profile

Cabenuva’s most common adverse effects include injection site reactions, rash, nausea, musculoskeletal pain, dizziness, headache, sleep disorder, fatigue, and fever. Although serious adverse effects are uncommon, they include hepatotoxicity, depression, and severe post-injection reactions. Cabenuva is contraindicated with the use of certain anticonvulsants, antimycobacterials, glucocorticoids, and St. John’s wort.⁵

Clinical Evidence

To date, there have been five key studies, three of them phase III trials of treatment-experienced individuals. ATLAS and ATLAS-2M studied treatment-experienced patients, whereas FLAIR (phase III), LATTE (phase II), and LATTE-2 (phase II) studied treatment-naive patients. Table 1 summarizes each study and its primary outcomes, and the phase III studies are summarized in the text that follows.

The ATLAS trial compared changing to monthly Cabenuva with staying on a three-drug oral ART regimen. ATLAS was a randomized, open-label trial with a total of 308 patients in the treatment and standard-of-care ART groups. At 48 weeks, 92.5% (n=285) had maintained virologic response in the Cabenuva group compared with 95.5% (n=294) in the three-drug oral ART group. Injection site reactions were common at 81% (n=250), but 99% of the reactions were grade 1 or 2, and 88% resolved within 7 days.⁸

The ATLAS-2M trial compared maintenance therapy Cabenuva every 4 weeks with every 8 weeks. There were 522 participants in the 8-week group and 523 participants in the 4-week group. Virologic response in the 8-week group was 94% (n=491) compared with 93% (n=484) in the 4-week group. The adverse event profile for each group was similar, and efficacy rates remained the same over 48 weeks, leading the investigators to conclude that every-other-month dosing would be appropriate. Of interest, the therapy was only FDA approved for a monthly dosing schedule.⁹

The FLAIR study compared the use of Cabenuva with oral three-drug ART in treatment-naive patients, with 283 patients in each group. Cabenuva had a 93.6% level of virologic response rate, compared with 93.3% with the three-drug therapy. Injection site reactions were common, but no other significant differences were found, leading the researchers to believe the long-acting injectable therapy was noninferior to the oral three-drug therapy.¹⁰

Conclusion

The combination of cabotegravir and rilpivirine presents as a new long-acting injectable maintenance therapy for patients with HIV-1 and could provide specific benefits related to adherence. This combination medication has been shown effective in both treatment-naive and treatment-experienced patients and, apart from injection site reactions, has an adverse event/risk profile similar to the other regimens currently available. However, clinical evidence is limited for Cabenuva, and more evidence should be gathered to establish its efficacy in specific patient populations, such as patients with other long-term health conditions. Even though Cabenuva is new to the market, its pricing compared with other agents indicated for maintenance therapy of HIV is competitive, making it accessible to patients sooner than expected (see Table 2).

Table 1. Summary of Results from Phase III Clinical Trials of Cabenuva

ABC = abacavir; ART = antiretroviral therapy; CAB = cabotegravir; DTG = dolutegravir; EFV = efavirenz; IM = intramuscular(ly); N/A = not applicable; NRTI = nucleoside reverse transcriptase inhibitor; PO = oral(ly); q = every; RPV = rilpivirine; 3TC = lamivudine.

Table 2. Dosing and Cost Information¹¹

AWP = average wholesale price.

References

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4. EDURANT oral tablets, rilpivirine oral tablets [product information]. Janssen (per FDA), 2018.

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7. Kerrigan D, Mantsios A, Gorgolas M, et al. Experiences with long acting injectable ART: a qualitative study among PLHIV participating in a phase II study of cabotegravir + rilpivirine (LATTE-2) in the United States and Spain. PLoS One 2018;13:e0190487.

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9. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet 2021;396:1994-2005.

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11. Cabenuva. RED BOOK (Micromedex®). Truven Health Analytics, 2021.