Experts Review Cabotegravir, Rilpivirine Therapy for Treatment of HIV Infections

During a presentation at the American Society of Health-System Pharmacists 2021 Midyear conference, the panelists reviewed long-acting (LA) antiretroviral therapies for the prevention and treatment of HIV infections, specifically a cabotegravir LA with rilpivirine LA intramuscular treatment.

Cabotegravir LA with rilpivirine LA is for the treatment of HIV-1 infections that is intended to replace antiretroviral regimens for those who are virologically suppressed on those regimens.

The individuals must have no history of unsuccessful treatment and no known or suspected resistance to either cabotegravir or rilpivirine.

“Cabotegravir/rilpivirine is actually already mentioned in the Department of Health and Human Services HIV guidelines,” Jennifer Cocohoba, PharmD, AAHIVP, BCPS, a professor and vice chair of faculty development in the department of clinical pharmacy at the University of California San Francisco, said during the presentation.¹

“It’s mentioned in 2 places. There is a separate statement on long-acting injectable antiretroviral regimens, specifically for cabotegravir/rilpivirine that was published earlier this year in February, soon after the medication was approved by the FDA, and there’s also a section on cabotegravir/rilpivirine LA in the management of the treatment-experienced patient, specifically in the section of optimizing therapy in the setting of viral suppression,” Cocohoba said.

The cabotegravir LA with rilpivirine LA is a monthly intramuscular injection with 400 mg of cabotegravir and 600 mg of rilpivirine. There is a loading dose of 600 mg and 900 mg, respectively.

There is also a 1-month, daily oral lead-in therapy of a 30 mg cabotegravir tablet and 25-mg tablet of rilpivirine before the loading injection.

Cocohoba discussed the 4 clinical trials of the injectable cabotegravir LA with rilpivirine LA: ATLAS, for maintenance therapy; ATLAS 2M, for extended interval; FLAIR, for the treatment-naïve; and LATITUDE, for use in individuals with medication adherence challenges.1

The ATLAS and FLAIR studies directly contributed to the FDA approval of cabotegravir with rilpivirine in January 2021.2

The FLAIR study was an open-label, phase 3, randomized study that included individuals who were treatment naïve. All the individuals were started on a 20-week regimen of a daily oral treatment regimen of abacavir, dolutegravir, lamivudine, or dolutegravir plus 2 other nucleoside reverse transcriptase inhibitors (NRTIs) if subjects were HLA-B*5701 positive)Some of the individuals stayed on the once daily oral treatments, while the other arm started the daily oral dose of cabotegravir with rilpivirine before undergoing the intramuscular treatment once a month. At week 96, the arm on the oral treatments was split into 2 additional arms: group 1 started the oral treatment, followed by intramuscular injections, and group 2 started the once-a-month intramuscular injection.

About 86.6% of individuals met the primary endpoint of HIV virologic suppression < 50 at week 96, while about 80.2% of individuals met the endpoint at week 124.1

There were just 5 individuals with confirmed virologic failure through week 124. Of these individuals, 4 had nucleoside reverse transcriptase inhibitor and integrase strand transfer inhibitor associated mutations.

The ATLAS study was also an open-label, randomized study, but it included individuals who were stable on an antiretroviral therapy (ART). ATLAS had the same endpoints as FLAIR.

There were 2 arms in this study where group 1 started the daily oral treatment of cabotegravir with rilpivirine for a month before the once-a-month intramuscular injection, and group 2 participants continued their baseline ART.

At week 48, about 92.5%of individuals on thecabotegravir with rilpivirine treatment achieved virological success, while about 95.5% of individuals met the primary endpoint while continuing their baseline ART.1

There were 3 individuals who had unsuccessful treatment on cabotegravir with rilpivirine.

“Similar to the FLAIR study, 2 of these 3 patients had resistance mutations to the nonnucleosides at baseline, perhaps impairing their ability to suppress and be successful on this regimen,” Cocohoba said during the presentation.1

There is an extension phase where investigators continue to gather data.

The ATLAS-2M study included individuals who were from the ATLAS study or individuals outside the ATLAS study who were receiving ART. Individuals who were outside the ATLAS study started on the daily dose of oral cabotegravir with rilpivirine.

Individuals were split into 2 groups, where group 1 either continued or was started on the standard cabotegravir with rilpivirine injection once every 4 weeks, while group 2 was started on cabotegravir 600 mg with rilpivirine 900 mg (or the loading dose) every 8 weeks.

The primary endpoint was to see if there was a detectable load at 48 weeks but has collected data up until 96 weeks.

About 91% of individuals on the loading dose every 8 weeks had virologic success, while about 90.2% of individuals on the standard cabotegravir with rilpivirine dosage had virologic success.1

There were 10 individuals with a lack of virologic success, and 6 of those individuals had resistance mutations.

In a post-hoc analysis of all 3 studies, the highest risk factor for a lack of virologic success was resistance at baseline, but other risk factors were the HIV subtype of A6 or a body mass index greater than 6.14 per square foot.

The LATITUDE study includes individuals who have difficulty to adhering to medications with a detectable viral load. The individuals will complete a standard of care ART for 24 weeks before being split into 2 arms.

Group 1 will continue ART, while group 2 will start the daily oral dosage of cabotegravir with rilpivirine for 4 weeks before moving onto the standard cabotegravir with rilpivirine injection.

Then, group 1 will be split again into the same two groups but at week 48.

The LATITUDE study is under way, and the results are pending.1

The most common adverse effect (AE) was injection site reactions.1 Other AEs included dizziness, fatigue, headache, musculoskeletal pain, nausea, pryexia, rash, and sleep disorders.

References

1. Cocohoba, J, Sherman, E. Long acting antiretroviral therapy for the treatment and prevention of HIV infection. Presented at: ASHP Midyear 2021. Accessed December 8, 2021.

2. FDA approves cabenuva and vocabria for the treatment of HIV-1 infection. FDA. Approval. January 27, 2021. December 9, 2021. https://www.fda.gov/drugs/human-immunodeficiency-virus-hiv/fda-approves-cabenuva-and-vocabria-treatment-hiv-1-infection