Scientific and Medical Consultant
Adjunct Clinical Professor of Medicine
Division of Infectious Diseases
Keck School of Medicine of USC
Los Angeles, California
W. David Hardy, MD, has disclosed that he has received funds for research support from Gilead Sciences, Janssen, Merck, and ViiV Healthcare and consulting fees from Gilead Sciences, Merck, and ViiV Healthcare.
Among noteworthy data presented at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) were results from 2 phase III studies of long-acting injectable cabotegravir (CAB) plus rilpivirine (RPV) as maintenance therapy: ATLAS and FLAIR. At Week 48, each study demonstrated a similar (noninferior) rate of maintenance of virologic suppression with monthly intramuscular 2-drug therapy vs daily oral 3-drug therapy.
At the end of April, based on these results, a New Drug Application was submitted for FDA review and approval of monthly injectable CAB plus RPV in patients who are virologically suppressed without history or evidence of resistance to regimen components. Pending a decision anticipated by late 2019, introduction of this unique drug delivery method will signal a new chapter in the evolution of ART with multiple benefits for people living with HIV.
Innovation has been a hallmark of the success of ART. Its first iteration approved in 2006, the single-tablet regimen (STR) transformed HIV care, drastically reducing pill burden and eliminating selective nonadherence. Now with more than 10 STR options at our disposal, we sometimes underestimate the adherence challenge that even a once-daily pill can pose for certain patients. There’s the burden of developing a foolproof reminder system, maintaining a current prescription, and keeping track of a pill bottle, including on vacation or in the context of a chaotic living arrangement such as homelessness. Long-acting injectable ART liberates patients from these daily processes, requiring one visit with 2 injections each month. For patients tasked with lifelong therapy, the difference between 12 and 365 days per year spent managing their HIV infection is substantial. Moreover, injectable regimens could be made available in centralized locations such as chain pharmacies or community-based organizations, handing back the onus of prescription management to the healthcare system that is much more adept at doing this.
Psychological Benefits and Patient Preference
Extending the interval between ART doses offers another appreciable advantage: freedom from the daily reminder of an HIV diagnosis. Healthcare providers may not fully appreciate this psychological stressor or the relief resulting from any strategy that mitigates it. In addition, without a daily pill to take, the risk of unintended disclosure of HIV infection to friends, family, coworkers, or even strangers is reduced. The patient-reported outcomes from ATLAS and FLAIR emphasize how positive this delivery strategy could be for people living with HIV. Although injection-site reactions (ISRs) did occur during 21% to 29% of injections, 99% were reported as mild to moderate in severity. Furthermore, only 1% of patients discontinued because of ISRs, and more than 97% of patients reported a preference for the long-acting regimen compared with daily oral ART. These data reinforce the acceptability of injectable therapy and encourage us as prescribers to refrain from prejudging what a patient may prefer.
Next Steps Toward Integration Into Care
What we saw at CROI 2019 will hopefully be only the beginning of a new phase of ART delivery. Long-acting injectable ART should remain a top priority for current and future ART development. I am already anticipating the day when ART regimens requiring injection or implantation at 3-month, 6-month, or even annual intervals will become reality.
ATLAS and FLAIR lay the scientific foundation for and open the door to a new era of long-acting injectable CAB plus RPV in persons with HIV. Provided this regimen receives FDA approval, it will be our responsibility to educate our patients about their options and work with them to select the therapy that best fits their lifestyle.
What did you take away from the ATLAS and FLAIR results? Join the discussion by posting a comment, or for more details on these and other key data from CROI 2019, check out full conference coverage from CCO here. Review study summaries, listen to Webinar audio, or download a comprehensive slideset. Then be sure to check back soon for CME/CE-certified expert analysis of the meeting from Dr. Daniel Kuritzkes and me.