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Treatment Paradigm Disruption With 2-Drug Regimens: Insights From IDWeek 2021

Karine Lacombe, MD, PhD

Sorbonne University
Head, Infectious Diseases Department
St Antoine Hospital, AP-HP
Paris, France

Karine Lacombe, MD, PhD, has disclosed that she has received consulting fees from Gilead Sciences, MSD, and ViiV Healthcare and has received other financial or material support from Chiesi, Gilead Sciences, MSD, and ViiV Healthcare.

View ClinicalThoughts from this Author

Released: November 2, 2021

In Western Europe, the arrival of 2-drug regimen (2DR) strategies has disrupted the prevailing paradigm of highly active antiretroviral therapy (ART) based on 3 potent drugs. Originally, many healthcare professionals may have questioned the intrinsic efficacy, patient convenience, and impact on comorbidities of such strategies as they considered treatment simplification to 2 drugs. However, in a meta-analysis and systematic review of 2- and 3-drug clinical trials (N = 5205 patients), Pisaturo and colleagues found that in treatment-naive patients with CD4+ cell counts >200 cells/mm3, both treatment strategies showed similar efficacy. New data presented at IDWeek 2021 also support the efficacy of 2DRs, reinforcing the need for practitioners in Western Europe to consider this treatment strategy in people with HIV.

Meta-analysis and Observational Analysis of 2DRs in Treatment-Experienced Patients
A meta-analysis by Evitt and colleagues regrouped observational data from virologically suppressed patients switching to dolutegravir (DTG)/lamivudine (3TC) and reported a >98% rate of sustained undetectability in the per-protocol analysis. However, a retrospective analysis of a subset of approximately 60,000 patients in the Trio Health HIV Research Network who received a 2DR showed that treatment-experienced, virologically suppressed patients switching to a 2DR combination of DTG/3TC or DTG/rilpivirine (RPV) had a higher risk of virologic failure than patients on a 3-drug regimen. Despite the limitations of this retrospective analysis, patients from observational cohorts may better reflect real-life behavior and therefore clinical efficacy, as these are patients different from those enrolled on clinical trials. Because 2DRs are such a hot topic in Western Europe right now, these observational data are a good reminder that appropriate patient selection and counseling prior to starting a 2DR are necessary for maximal effectiveness.

Use of 2DRs in Patients With Chronic Kidney Disease
DTG/RPV is the only 2DR not needing dose adjustment in patients with chronic kidney disease (CKD). To study the efficacy and safety of 2DRs in patients with CKD, a retrospective chart review of 36 Black patients receiving a 2DR at the HIV clinic at SUNY Downstate Health Sciences University was performed. Kang and colleagues found that suppressed HIV-1 RNA at 6 months was achieved in 81.8% of patients with an estimated glomerular filtration rate <60 mL/min and 92.9% of patients with an estimated glomerular filtration rate >60 mL/min. These data are reassuring and support offering a simplified regimen to our patients in Western Europe who are more vulnerable because of concomitant CKD.

Long-Acting 2DRs
Combining the concept of 2DRs with that of long-acting highly active ART has driven the development of cabotegravir (CAB)/RPV, where simplification and convenience are combined to enhance patient adherence without compromising virologic efficacy. At a Ryan White–funded HIV clinic, a pilot long-acting ART program was launched with the objective of describing the cascade of care and barriers to treatment access. Collins and colleagues found that some patients had to discontinue their proton pump inhibitor before receiving the oral RPV lead-in, and others were denied treatment by their insurance or were found to have an acquired resistance to RPV, which precluded the use of the long-acting 2DR. These findings highlight the concerns about delayed access to long-acting 2DRs if potential barriers are not anticipated.

However, concerns about injection frequency, adverse events, and the need for a clinic visit every month also exist. Semistructured phone interviews conducted in a group of 34 patients from the CUSTOMIZE study revealed that those concerns quickly disappeared with time, and the fear of potential adverse events was largely exaggerated before treatment initiation.

In a larger group of US and Canadian patients from the FLAIR, ATLAS, and ATLAS-2M phase III/IIIb trials (N = 376), which all evaluated long-acting CAB/RPV, efficacy, safety, and tolerability were optimal. Most participants preferred the long-acting 2DR over their previous regimen. These studies suggest that CAB/RPV also may be a potential therapy for many patients in Western Europe who wish to use long-acting 2DRs.

Your Thoughts?
How will the results of these studies influence your decision to prescribe 2DRs for your patients with HIV? Join the discussion by posting a comment. For more details on this and other key HIV issues from IDWeek 2021, review more CCO Conference Coverage, including Capsule summary slidesets, video recaps with expert faculty, and other ClinicalThought commentaries highlighting US and global perspectives.

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