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ClinicalThought: ART Resistance
ART Resistance: New Data From EACS 2021

Released: November 23, 2021

Expiration: November 22, 2022

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Several presentations at the 18th European AIDS Conference (EACS 2021) in London shed light on antiretroviral drug resistance in contemporary HIV care. Here’s my recap of the most important data you should know.

Declining Multidrug Resistance
First was the good news of a decline in multidrug resistance across Europe reported by Dewandre and colleagues. The greatest change occurred in 4-class resistance, which declined from 0.15% in 2010 to 0.03% in 2019. This progress is likely linked to steady improvements in efficacy, resistance barriers, tolerability, and convenience of antiretroviral regimens, which have impacted options across the treatment spectrum from naive to highly treatment experienced patients.

Archived Resistance and Antiretroviral Therapy Switching
Routine HIV practice often involves switching already suppressed patients to ensure optimal, simplified, personalized treatment, and guidelines generally favor regimens containing 2 (selected) or 3 fully active drugs. EACS 2021 extended our evolving understanding of the impact of archived resistance in suppressed patients.

Specifically, real-world data presented by Micán and colleagues was consistent with previous clinical trial data showing that virologically suppressed patients with archived resistance to nucleos(t)ide reverse transcriptase inhibitors generally maintain viral suppression if switched to bictegravir (BIC)/tenofovir alafenamide (TAF)/emtricitabine (FTC). Andreatta and colleagues reported similar results in those suppressed on boosted protease inhibitors or with viral blips. Also, on the issue of archived resistance, Hocqueloux and colleagues found that archived M184V mutations did not increase risk of virologic failure after switching to dolutegravir (DTG) plus lamivudine (3TC) 2-drug therapy. Nevertheless, use of DTG/3TC in patients with known archived M184V mutation remains controversial in routine practice while clinical studies continue.

Adherence and Antiretroviral Therapy Outcomes
Antiretroviral drugs with novel mechanisms of action circumvent resistance to other classes and are being incorporated into salvage regimens. However, adherence remains critical for success. Data from the randomized phase III BRIGHTE study showed preserved susceptibility to DTG, darunavir, and etravirine in most patients failing fostemsavir-containing salvage regimens, suggesting ongoing suboptimal adherence. This emphasizes the importance of sustained adherence counseling and practical assistance across the treatment continuum, regardless of regimen.

Simulation of multiple missed doses of recommended daily second-generation integrase-based regimens (BIC/TAF/FTC, DTG plus TAF/FTC, DTG/3TC, and DTG/rilpivirine RPV) provided a reminder that all regimens are at risk of viral rebound and resistance in poorly adherent persons, although the risk varies. In this in-vitro study, BIC/TAF/FTC had the greatest forgiveness and barrier to resistance, and DTG/RPV had the least.

Investigational Antiretroviral Regimens
What is in the horizon? In the phase IIb study of the 2-drug regimen of islatravir plus doravirine, none of the 121 study participants met the criteria for resistance testing through Week 144. More data on the resistance profile of this 2-drug regimen will come from ongoing phase III studies.

On the other end of the treatment spectrum, lenacapavir showed great promise in patients with multidrug resistance and limited treatment options, although resistance mutations emerged in a few individuals whose salvage regimen appeared to have lenacapavir as the only active agent, providing a reminder of the failure and resistance risks of antiretroviral monotherapy in any context.

Your Thoughts?
Which new data on antiretroviral drug resistance will most influence your management of persons living with HIV? Answer the polling question and join the conversation by posting in the discussion section. For more from EACS 2021, download Capsule Summaries of these and other key studies and watch on-demand webcasts featuring expert insights on the clinical implications of the latest data.

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Approximately what percentage of the patients in your clinic have multidrug resistance?
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