Two pills a week or two shots a month

Islatravir plus lenacapavir

“The combination of islatravir (ISL) and lenacapavir (LEN) has the potential to become the first weekly oral complete regimen for the treatment of HIV,” said presenter Amy Colson, MD, MPH, of the Community Resource Initiative (CRI), in Charleston, Massachusetts.

Islatravir plus lenacapavir successfully maintained viral suppression (undetectable viral load) in treatment-experienced people.

The study, NCT05052996, is still early. It’s in Phase 2, and the results are only out to 24 weeks (six months). It enrolled people who had stable undetectable viral load while on Biktarvy, arguably the most commonly taken HIV treatment in the U.S.

Fifty-two individuals were switched to weekly therapy. Another 52 persons continued taking their Biktarvy, for comparison purposes, as a control group.

At 24 weeks, 94.2% of the ISL + LEN group had maintained their undetectable viral load. This compared to 92.3% of the Biktarvy group who had stayed undetectable. (The figure was actually 100% of the people on Biktarvy, but there was some lack of data as a result of dropouts or missing study visits. This happened in both groups—two individuals, or 3.8%, for the weekly group and four individuals, or 7.7%, for the Biktarvy group.)

One person in the weekly group had low-level detectable virus at the six-month mark (an HIV RNA of 251 copies). This individual stayed on the therapy and regained viral suppression at 30 weeks (less than 50 copies).

The most common adverse events seen in the ISL + LEN group included arthralgia (joint stiffness) and fatigue (three individuals each, 5.8%), diarrhea (7 individuals, 13.5%) and upper respiratory infections (6, 11.5%).

Islatravir is part of a new class of HIV medications not yet on the market—nucleoside reverse transcriptase translocation inhibitors (NRTTIs). Lenacapavir is also from a new drug class, capsid inhibitors (CAIs). Lenacapavir is already on the market as a once-weekly injection, under the brand name Sunlenca. The two medications are being studied in both oral and injectable formulations. Both drugs are also being studied for HIV prevention (PrEP).

To read the study abstract (summary), GO TO bit.ly/3QlOFds. For the webcast presentation, GO TO bit.ly/49Pb4He.

Cabenuva works for people with detectable viral load

The LATTITUDE study showed that people with problems taking their oral therapy can reach the holy grail of undetectable viral load using Cabenuva, the long-acting injectable HIV treatment that is a complete regimen by itself. (See February+March, Briefly.) 

LATTITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life), also known as the ACTG A5359 study, showed success with using Cabenuva as two long-acting injectables once a month. (Cabenuva can also be used just every other month.)

Sure, that’s standard today out in the real world with Cabenuva. But this study was for people who had challenges taking their oral medication, a group that’s usually excluded from HIV drug studies. Currently, the U.S. Food and Drug Administration (FDA) requires that people have suppressed viral load (be undetectable) before they can be given Cabenuva.

At a CROI press conference, presenter Aadia Rana, MD, of the University of Alabama, put aside the data for a moment to make clear the promise of the LATTITUDE study.

“Our hope is that this study will expand the HIV treatment guidelines for long-acting injectable treatment to include people with a history of non-adherence and influence the payer decisions,” Dr. Rana said. “I'm tremendously excited, in addition, that this study is a clear demonstration that large, randomized treatment trials in a population with challenges to adherence can be successfully done. It is a call to action to include these populations, historically described as hard to reach, earlier in the process of drug development, particularly in the long-acting therapeutic space.

“Our next challenge,” she added, “is to continue implementation of this strategy in those who have benefited most.”

ACTG, a clinical trials group based in the U.S. which historically studies HIV, looked to Cabenuva to fill a special need.

“Only about 65% of people with HIV diagnosed in the U.S. are estimated to be virally suppressed on daily oral tablets due to issues including mental health and substance use challenges, competing responsibilities and financial constraints and stigma,” said Dr. Rana.

“The ACTG LATTITUDE study, which started enrolling participants in March 2019, compared monthly injectable HIV medications, cabotegravir plus rilpivirine, to daily oral tablets in people with HIV who had a history of challenges taking their daily medications. Participants in this study first received comprehensive adherence support, including conditional financial incentives, to achieve viral suppression on oral therapy. Of those who are successful in achieving viral suppression, they were then randomized to monthly injections or to continue on their daily oral pills for approximately one year,” Dr. Rana explained. “At a planned review of this study conducted [in February] by an independent safety monitoring board, the monthly cabotegravir and rilpivirine injections were found to be more effective in suppressing HIV compared to daily pills. The board recommended halting randomization and offering all participants long-acting injectable therapy.

“This study is critically important because it shows that long-acting injectable HIV medications can provide substantial benefit to a broader population than those covered by the current regulatory approvals, including those by the U.S. FDA,” Dr. Rana said. “If guidelines were to recommend such broader use, it would be expected to have a larger impact on rates of new HIV infections, as most are transmitted by persons with HIV who are aware of their diagnosis but are not virally suppressed.” 

Read the abstract (Abstract 212), GO TO bit.ly/3JCnjfB.