Long-acting Cabenuva (injectable cabotegravir and rilpivirine) is more effective than daily antiretroviral pills for people who have had difficulty achieving consistent adherence and maintaining viral suppression, according to an announcement from ViiV Healthcare.

The company said that after reviewing interim results, the data safety and monitoring board for the LATITUDE trial recommended that randomization should be stopped and study participants taking daily pills should be offered the long-acting injectables. The announcement did not include detailed data, which ViiV said would be presented at an upcoming conference.

[UPDATE: Study results were presented on March 6 at the Conference on Retroviruses and Opportunistic Infections in Denver.)

“There are many reasons why people may find it challenging to stay on daily oral treatment, and the LATITUDE study shows cabotegravir and rilpivirine injectable treatment can help them keep their virus suppressed, which benefits their overall health,” Kimberly Smith, MD, MPH, head of research and development at ViiV, said in a company press release. “Optimizing therapy for all people living with HIV, including those with adherence challenges, is critical to the effort to end the HIV epidemic.”

All modern antiretroviral regimens are highly effective and generally well tolerated, so treatment success often comes down to consistent use. Some people have difficulty maintaining good adherence because they forget to take their pills or don’t want to think about HIV every day, are concerned about having pill bottles that could reveal their HIV status or are in living situations where their pills could be lost or stolen. About a third of people with diagnosed HIV in the United States do not have viral suppression, which means they are at risk for disease progression and could transmit the virus to their sex partners. For some of these individuals, long-acting treatment may be a better option.

Approved in 2021, Cabenuva is the first complete antiretroviral regimen that does not require daily pills. The treatment involves two intramuscular injections in the buttocks administered by a health care provider once monthly or every two months; an oral lead-in of cabotegravir and rilpivirine pills is optional. Cabenuva is approved for people with viral suppression who have no history of treatment failure and no known or suspected resistance to either drug. (Injectable cabotegravir alone, sold as Apretude, is approved for HIV pre-exposure prophylaxis.)

As reported at the 2019 Conference on Retroviruses and Opportunistic Infections, two Phase III clinical trials showed that the long-acting injectables work as well as daily pills. The ATLAS study evaluated Cabenuva as maintenance therapy for treatment-experienced people with an undetectable viral load on a standard oral regimen. They were randomly assigned to either stay on their daily regimen or switch to monthly injections after an oral lead-in. Virological response rates were 96% and 93%, respectively, showing that Cabenuva was non-inferior to continued oral therapy. The FLAIR study enrolled previously untreated people who briefly used an oral regimen to achieve viral suppression before being randomized to either stay on the pills or switch to Cabenuva. Response rates were again comparable, at 93% and 94%.

Since that time, other research has looked at refinements to the injectable treatment. The ATLAS-2M and SOLAR trials showed that administering the injections every other month works as well as once-monthly dosing. The Food and Drug Administration (FDA) has approved both dosing schedules. Another study showed that the oral lead-in is not necessary.

The LATITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life) trial (NCT03635788), sponsored by the National Institutes of Health (NIH) and run through the ACTG clinical trials network, focuses on people who face challenges taking a daily oral regimen and have evidence of detectable virus. Launched in 2019, the study is ongoing at 31 sites in the United States, including Puerto Rico.


Participants were screened to ensure that their HIV was not resistant to the study drugs and that they met other health and safety criteria. They started on a standard three-drug oral regimen, receiving comprehensive adherence support and economic incentives to achieve viral suppression. Eligible participants were then randomly assigned to either continue on the same daily regimen or switch to Cabenuva, with or without the optional oral lead-in, administered once monthly for a year. (The every-other-month dosing schedule was not used in this study.)

Based on a planned interim review on February 12, Cabenuva “demonstrated superior efficacy in maintaining viral load suppression compared to daily oral therapy in individuals with a history of [antiretroviral therapy] adherence challenges,” according to the ViiV announcement.

Study participants are being notified of these findings, and those currently taking daily oral antiretroviral therapy will decide with their providers which method suits their needs best, according to an NIH statement. All study participants will be monitored for another year. 

As noted, Cabenuva is only FDA-approved for people with an undetectable viral load. LATITUDE participants received support to achieve viral suppression on a daily oral regimen before switching to the injectable regimen, so the study results do not apply to people who are unwilling or unable to take pills consistently and cannot get their HIV under control. Pilot studies, however, show that long-acting injectables are also a feasible option for people without viral suppression, if offered with adequate support.

 

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