General Information

Cabenuva (cabotegravir and rilpivirine, injectable formulation) is a once-monthly, long-acting (extended release) regimen combining the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV Healthcare, with rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Janssen Sciences Ireland UC.

Vocabria (cabotegravir, tablet formulation), is designed to be taken in combination with oral rilpivirine (Edurant) for one month prior to starting treatment with Cabenuva to ensure the medications are well-tolerated before switching to the extended-release injectable formulation.

Cabenuva is specifically indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace a current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.

Cabenuva should be administered by a healthcare provider once-monthly as two individual intramuscular injections in the buttocks. Prior to initiating treatment with Cabenuva, oral cabotegravir (Vocabria) and oral rilpivirine (Edurant) should be administered for approximately one month to assess the tolerability of each therapy.

Clinical Trials

The FDA approval of Cabenuva was based on the pivotal Phase 3 ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen) studies that included more than 1,100 patients from 16 countries, including the U.S. The studies demonstrated that Cabenuva was as effective as continuing a daily, oral, three-drug regimen in maintaining viral suppression throughout the 48-week study period.

In the ATLAS study, Cabenuva met the primary endpoint for noninferiority (the proportion of participants with plasma HIV-1 RNA ≥50 copies per milliliter [c/mL] at Week 48), with a comparable number of patients receiving either Cabenuva or their daily current antiretroviral regimen (CAR) having an HIV-1 RNA level ≥50 c/mL. Two percent of patients receiving the long-acting injectable and 1% of patients receiving CAR had an HIV-1 RNA level ≥50 c/mL at Week 48 (Treatment Difference 0.7%).

In the FLAIR study, at Week 48, a comparable number of patients receiving either Cabenuva or daily oral dolutegravir/abacavir/lamivudine therapy had an HIV-1 RNA count ≥50 c/mL, meeting noninferiority criteria. Two percent of patients in both treatment arms had an HIV-1 RNA count ≥50 c/mL at Week 48 (Treatment Difference -0.4%).

Mechanism of Action

INSTIs, like cabotegravir, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection.