Long-Acting AntiRetroviral Therapy (ART) Can Be Considered Part of AIDS Arsenal
Presenter: Eric S. Daar, MD, Harbor-University of California, Los Angeles (UCLA) Medical Center, Los Angeles, CA, United States
A summary of The Science: Understanding the Tools in Our Arsenal from the session Honing Clinical Skills in HIV Treatment: Considering the Patient, the Provider, and the Science, presented July 18, 2021, at the 11th International AIDS Society (IAS) Conference on HIV Science.
Novel, long-acting antiretroviral therapy (ART) formulations are poised to change how clinicians manage patients with AIDS. Until now, all treatment regimens have required daily dosing, at a minimum, and have included second-generation integrase inhibitors, with two-drug regimens preferred. There have been multiple advances in recent years both in treatment strategies and ART regimens. These new long-acting ART regimens are promising for patients who are virologically suppressed, struggle with daily therapy (inconsistent), or have multidrug resistance, according to Eric S. Daar, MD, Professor of Medicine at David Geffen School of Medicine at University of California, Los Angeles.
Recommended for the first time, long-acting ART, a dual-drug intragluteal injection, has been approved for use every 4 weeks in the United States, and an injectable therapy has been approved for use every 8 weeks in Europe.
Long-acting cabotegravir/rilpivirine (CAB/RPV) was recently approved in the United States and select countries for virally suppressed patients with no history of virologic failure. The most common reasons for switching ART include regimen simplification, management or prevention of toxic effects or comorbidities, avoidance of interactions with drugs or food or supplements, and economic factors. With studies showing that long-acting ART maintains levels of suppression in the 93% range, “Patients appear to tolerate it well, and treatment satisfaction is quite high,” said Daar.
“Typically, injectables can maintain high levels of drug concentration for a long time, and these injectables can maintain sufficient levels of both drugs after injection to allow for dosing as infrequently as every 4 weeks. This is the first time we have the potential for truly long-acting therapy,” noted Daar.
In addition, the Antiretroviral Therapy as Long-Acting Suppression (ATLAS)-2M study reported that after 48 weeks of therapy, a long-acting CAB/RPV injection every 8 weeks was non-inferior to injections every 4 weeks.
Switching drugs based on resistance is one of the most common strategies in clinical practice. Switching from an oral drug to a long-acting injectable is now another consideration with a new, first-in-class, capsid inhibitor developed for treatment-experienced patients in the later stages of development. This subcutaneous injection has a long half-life and the potential to be administered every 6 months. “This is a new drug in a new class for those with underlying resistance. It’s another drug that could be incorporated into a long-acting regimen,” said Daar.
Daar outlined the advantages and disadvantages to consider with long-acting ART. The advantages include less frequent dosing, fewer adverse events, fewer drug-drug interactions, no pill burden, high bioavailability, reduced stigma associated with taking pills daily, and increased adherence. The disadvantages include concern for pregnant patients, emerging resistance, and patients who are inconsistent with visits; the need for combining with an oral regimen for those infected with hepatitis B; complicated criteria to resume if patient is noncompliant; and risk of virologic failure, particularly with nonadherence.
“The switch to long-acting drugs is not a straight-forward decision. It is crucial to discuss the advantages and disadvantages with patients while weighing optimal patient selection and implementation strategies for recently approved long-acting therapies,” said Daar.
Disclosures
Eric S. Daar, MD, reported consulting fees: Gilead Sciences, Inc., Merck & Co., Inc., and ViiV Healthcare Limited and contracted research: Gilead Sciences, Inc. and ViiV Healthcare Limited.
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