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Why Long-Acting ART is the Latest Game Changer for HIV Treatment

Jean-Michel Molina, MD, PhD

Head of the Department of Infectious Diseases
Saint-Louis Hospital, Assistance-Publique Hôpitaux de Paris
Paris, France
Professor of Infectious Diseases
University of Paris
Paris, France


Jean-Michel Molina, MD, PhD, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, Merck, and ViiV Healthcare and funds for research support from Gilead Sciences.


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Released: November 30, 2021

There is no question that HIV treatment has made astounding progress during the past 25 years―from the initial days of single-drug and dual-drug treatments with harmful adverse events (sometimes causing lasting changes in physical appearance) and rapid emergence of drug resistance to more effective regimens involving complex triple-drug strategies that required multiple tablets dosed several times per day (also with considerable toxicity and tolerability challenges vs what we have now) to a plethora of highly effective, safe, and tolerable regimens that have a high genetic barrier to resistance and often involve only a single tablet taken once per day. Modern-day HIV regimens allow a lifetime of complete viral suppression with essentially no risk of transmitting HIV to sexual partners. Nonetheless, HIV treatment coverage still is incomplete, primarily due to a combination of system limitations and sociodemographic barriers that warrant further improvements in both treatment delivery options and healthcare systems. One such improvement has recently emerged, with further enhancements on the horizon: long-acting antiretroviral therapy (ART).

Why is Long-Acting ART Needed?
Although single-tablet regimens work extremely well and meet the treatment needs of many people with HIV, they are not a panacea. What are the drawbacks of a single daily pill? For a substantial number of patients, the answer relates to the stigma of having HIV. Many young, otherwise healthy individuals with HIV describe the psychological burden of having to take a daily pill for HIV treatment―a constant reminder that they have an incurable disease associated with a long history of discrimination. This also is true for older patients who may take other daily medications but still would prefer that their HIV medication not be included in that regimen. The pills also represent the risk of unwanted disclosure―a physical representation of HIV status. We learned a great deal about patient preferences and needs from the phase III trials of injectable cabotegravir plus rilpivirine, the first available long-acting regimen approved as a switch strategy for patients with viral suppression on their current oral regimen. Although the long-acting regimen involved 2 IM injections every 1-2 months, the vast majority of patients in the trials preferred not having to take daily pills and did not want to go back to oral pills for their HIV treatment at the end of the studies. For these reasons, long-acting therapy represents the next step in improving patient lives by responding to their needs and preferences regarding HIV treatment. Until we have a true cure for HIV, long-acting treatment offers the closest psychological semblance of being cured, allowing people to forget about their HIV for a time in the absence of the daily pill reminder.

What Does Long-Acting ART Look Like Now and in the Future?
As mentioned, 1 long-acting option is currently available: long-acting cabotegravir plus rilpivirine administered as IM injections every 1-2 months, depending on the approval indication in different countries. However, many strategies are under intensive investigation. Based on what currently is being evaluated in clinical trials, what could long-acting ART look like in the future? Pending safety and efficacy results from studies of these investigational strategies, it is possible that future long-acting ART options could be quite diverse, including some or all of the following.

  • Oral dosing once per week (islatravir, lenacapavir)
  • SC injection every 6 months (lenacapavir)
  • Implants replaced every 6-12 months (islatravir)
  • IV injections 2-4 times per year (combinations with broadly neutralizing HIV antibodies)
  • Microneedle array patches replaced every several months (bictegravir)

In considering the diversity of options in clinical studies, it is safe to say that we are at the beginning of the age of long-acting HIV treatment options, and the future is very promising. Of most importance, the evolution of HIV therapy continues to be driven by patient needs and desires, bringing treatment closer to a full sense of clinical cure.

Your Thoughts?
Which investigational long-acting ART strategy are you most hoping to offer your patients in the future? Answer the polling question and join the discussion by posting a comment. For more discussion of HIV treatment and to see currently available data on investigational long-acting ART strategies, download the slides and watch the webcast from our recent satellite symposium at the 18th European AIDS Conference, “Individualized Choices in Antiretroviral Therapy: Present and Future.”

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