New Guideline for Replacement ART: CAB/RPV LA Not for Everyone

“One of the most important considerations before switching HIV patients to injectable long-acting cabotegravir/rilpivirine [CAB/RPV LA; Cabenuva, ViiV Healthcare] is for the patient and the clinician to arrive at this decision together,” Elliot DeHaan, MD, told Medscape Medical News. “This therapy is not necessarily for everyone.”

DeHaan is lead author of the newly released clinical guideline from the New York State Department of Health AIDS Institute for use of CAB/RPV LA as replacement antiretroviral therapy (ART) in virally-suppressed adults with HIV. He explained that the guidance expands upon Health & Human Services’ February 24 CAB/RPV LA recommendations, highlighting some of the most important clinical and patient considerations necessary to implement injectable ART. “There are a lot of things that need to be laid out beforehand,” he said.

Gaining Consensus

Approved by the FDA in late January 2021, CAB/RPV LA is considered an optimization strategy for individuals with HIV whose virus is suppressed by oral ART and who might prefer monthly injections versus daily oral therapy. While there are various reasons why patients might wish to switch to a long-acting injectable, one of the primary concerns is adherence. Of note, the guidance points to phase 3 clinical study findings that suggest high levels (86% to 91%) of patient satisfaction with CAB/RPV LA, which portends a promising future for this therapeutic approach.

With regard to patient preference, recommendations focus on the need to thoroughly discuss several critical requisites with potential candidates, including a 4-week lead-in daily oral ART course (CAB [Vocabria] 30 mg, RPV [Edurant] 25 mg) before initiating a loading dose. Patients should be advised of the potential for development of resistance should dosing be interrupted for any reason (CAB and RPV have extended half-lives ranging from mean 5.6-11.5 weeks for CAB and 13-28 weeks for RPV), as well as the need to return to oral bridging therapy if subsequent injections are not administered within the 7-day window period. If the maintenance dose is delayed beyond 2 months, a loading dose and restart is necessary.

CAB/RPV LA therapy is administered into opposing gluteal muscles (CAB into one gluteus medius and RPV into the contralateral gluteus medius) and injection-site pain beginning 1 day post-injection and lasting 3-4 days is common. In phase 3 clinical trials, as many as 83% of patients experienced adverse effects (AEs), which also include nodules, induration, and swelling at the injection sites. Fortunately, 99% of AEs were of mild to moderate severity. While pain tends to decline over several injections, DeHaan said that it’s an important part of the initial discussion about switching therapies.

Other Considerations

Prior resistance testing, ART treatment history, and/or baseline genotypic resistance testing that includes both reverse transcriptase and integrase genes should be reviewed or conducted before initiating treatment. K103 mutations alone are not considered exclusionary. Virologic failures (defined as two consecutive plasma HIV-1 RNA measurements > 200 copies/mL), while rare, were reported in 13 clinical trial participants. Recent data suggest that patients who developed resistance despite adherence had at least two of three factors: a body mass index > 30 kg/m2, the HIV-1 subtype A6/A1, and the presence of proviral RPV RAMS.

CAB/RPV LA does not treat hepatitis B (HBV) co-infections, reinforcing the need for concurrent oral HBV therapy.

And there’s a paucity of data on the safety and efficacy of CAB/RPV in children, adolescents, or during pregnancy/lactation, precluding its use in those patient populations.

Clinical, Institutional Considerations

Adaptation of CAB/RPV LA as ART requires specific clinical institutional planning, especially in light of current pandemic-related resource and staffing limitations. Monthly dosing must be done within a 7-day window and requires preparations akin to initial loading doses. In addition to pharmacy resources and onsite storage requirements, the guidance points to patient scheduling and reminder systems, access (patient transportation, work constraints, parking), and most importantly, contingency plans for care (including oral bridging therapy) should a clinic be forced to shut down for any reason. Additional factors include billing protocols, insurance or third party authorizations, and provision of counseling and education training.

“Given that this is a completely new way of thinking among providers, we’re all learning together,” said David Koren, PharmD, MPH, a clinical pharmacy specialist in infectious diseases at Temple University in Philadelphia, Pennsylvania. “The guidelines provide a nice framework for taking the next step to operationalize these processes into practice, taking into account that barriers to implementation are still unknown.” Koren was not involved in the development of the guidelines.

DeHaan has disclosed no relevant financial relationships. Koren disclosed serving on a prior Advisory Panel for ViiV Healthcare US.

Liz Scherer is an independent journalist specializing in infectious and emerging diseases, cannabinoid therapeutics, neurology, oncology, and women’s health.

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