Editor’s Note:
In 2021, the United Nations set forth the goal of “ending the AIDS epidemic by 2030”. To achieve this, not only must countries strengthen the diagnosis and treatment of HIV infections, but they also need to prioritize prevention to minimize the emergence of new infections. Pre-Exposure Prophylaxis (PrEP) long-acting regimens have become a recent focal point in HIV prevention. At the recently held 12th International AIDS Society HIV Science Conference (IAS 2023), there were several keynote lectures on the topic of long-acting PrEP. Infectious Disease Frontier had the privilege to interview Dr. Deborah Donnell from the Vaccine and Infectious Disease Division of the Fred Hutchinson Cancer Research Center at the University of Washington, who shared her insights on the challenges faced in HIV prevention and the characteristics of the new long-acting PrEP regimen.
Infectious Disease Frontier: The latest UNAIDS data shows that there were still 1.3 million new HIV infections in 2022. What challenges do you think still exist in the current HIV prevention measures (including PrEP and PEP)?
Dr. Donnell: I think the main difficulties are really about implementation. We have drugs that work, but we’re facing challenges in implementing them and ensuring they reach those who need them, to prevent new infections from occurring. It’s a significant challenge determining how to deliver these drugs to those who need them for prevention.
Infectious Disease Frontier: What are the advantages of current Long-acting PrEP such as cabotegravir (CAB) compared to oral PrEP? Simultaneously, what are the shortcomings of the current Long-acting PrEP?
Dr. Donnell: The advantages, from the participants’ perspective, include not having to take a daily pill. An injection once every 8 weeks is all that’s needed, freeing them from having to think about their HIV prevention daily. The primary limitation currently appears to be the clinical implementation. Administering intramuscular injections in a clinical setting for prevention has proven more complicated than initially anticipated. Another challenge we’re facing is the drug’s production. I hope this is just a temporary setback, but it’s one of the factors hindering us from widespread prevention. These seem to be the main advantages and limitations.
Infectious Disease Frontier: Apart from CAB, what other PrEP approaches do you believe hold promise for the future? Aspects like reduced injection volume, alternate formulation type, different routes of administration, extended dosing intervals, and a shortened PK tail come to mind.
Dr. Donnell: I believe that any approach requiring less effort from the participant and costing less will be worth pursuing. For instance, lenacapavir is currently under testing, and it only needs an injection every 6 months. For many, visiting the clinic twice a year is more manageable than six visits. Formulations with extended action might have a long tail. Being able to remove the drug through methods like patches or implants would appeal to those uneasy about having the drug in their system for extended periods. Still, I believe all these new formulations are worth pursuing, as we currently are.
Infectious Disease Frontier: How could these new biologics potentially transform HIV prevention strategies in the future?
Dr. Donnell: The aspiration for these new long-acting biologics is transformative – hoping to locate the resources and resolve the clinical implementation issues so that everyone at risk for HIV can have access to a long-acting antiretroviral, enabling them to lead their lives without the risk of HIV. I believe these long-acting prevention products truly have that potential.