HIV

Olivia C. Welter, PharmD

In March 2024, the International Antiviral Society–USA (IAS-USA) guidelines panel issued a letter to JAMA to provide an updated HIV treatment recommendation for use of long-acting injectable cabotegravir and rilpivirine (CAB-RPV). 

This updated recommendation is the result of several studies conducted since the IAS-USA treatment guidelines were originally published in 2022. They add to a growing body of evidence demonstrating long-acting injectable CAB-RPV is a safe and effective course of therapy for certain patients with HIV viremia.

In the original December 2022 publication of the IAS-USA HIV treatment guidelines, limited evidence existed to prove injectable CAB-RPV is an acceptable option for patients with HIV viremia. Because of this, and the potential for antiretroviral resistance, the IAS-USA guidelines panel only recommended injectable CAB-RPV for patients who have achieved viral suppression.

However, several studies have since investigated the utility of injectable CAB-RPV in patients with HIV viremia who are unable to take or adhere to oral antiretroviral therapy. One study published on July 4, 2023, in Annals of Internal Medicine by Gandhi and colleagues reported that 94% of patients achieved and maintained viral suppression while being treated with injectable CAB-RPV in addition to intensive case-management services.

Updated recommendation for injectable CAB-RPV

With the observed success of injectable CAB-RPV in patients with HIV viremia, the updated recommendation from IAS-USA guides clinicians to consider injectable CAB-RPV in addition to intensive follow-up and case management services for patients with viremia who meet certain criteria when no other treatment options are effective. Injectable CAB-RPV can be dosed every 2 months.

Criteria include a patient being persistently unable to take oral antiretroviral therapy despite extensive efforts and clinical support, high risk of HIV disease progression defined as CD4 cell count <200/μL, or history of AIDS-defining complications, and the virus being susceptible to both CAB and RPV.

These criteria indicate that, while injectable CAB-RPV can be a preferred treatment option for certain populations, clinical guideline developers such as IAS-USA will likely hold off on making it a gold standard treatment recommendation until randomized clinical studies can be conducted with adequate sample sizes.

Additional findings

Several organizations and research teams have recently presented and published their findings on injectable CAB-RPV use. An abstract presented by Rana and colleagues at the March 2024 Conference on Retroviruses and Opportunistic Infections concluded that injectable CAB-RPV demonstrated superior efficacy compared to the daily oral standard of care for HIV treatment in people with HIV who have adherence challenges.

Pivoting to look at safety rather than efficacy, an organization called aidsmap has advised clinicians to exercise caution when prescribing injectable CAB-RPV and to be mindful of drug resistance potential. While many studies show high rates of viral suppression from the therapy, there is a small number of patients who develop drug resistance and therefore have limited remaining treatment options.

Future considerations

The IAS-USA treatment guidelines panel noted in their letter to JAMA that there are currently no randomized clinical studies that exist to support the updated recommendation for injectable CAB-RPV use in patients with viremia. Current evidence is also limited in its reliability due to small numbers of study participants, variable dosing regimens, and ill-defined clinical supports. The guidelines panel encourages clinicians to refer their eligible patients to prospective clinical trials so more data can be collected.  ■