From CROI 2022: Week 152 ATLAS-2M Results on LA ART and Implications for Patients

The Week 152 results of ATLAS-2M presented at the 2022 Conference on Retroviruses and Opportunistic Infections (CROI) showed that virologic suppression rates remained high with 85.9% and 87.4% in the every-4-week (Q4W) and every-8-week (Q8W) dosing arms, respectively, of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) in the intention-to-treat, exposed population. Only 2 patients developed confirmed virologic failure (CVF) between Weeks 96 and 152 and both were in the Q8W arm. They failed with high HIV-1 RNA levels of 24,221 and 59,467 copies/mL and emergent resistance mutations to RPV and integrase strand transfer inhibitors. This brings the total number of patients with CVF in ATLAS-2M to 13: 11 (2%) in the Q8W arm and 2 (<1%) in the Q4W arm. A deeper dive into the characteristics of the patients with CVF showed that the failures could not be explained by missed doses; in fact, none of the 13 persons with CVF so far has had more than 7 days of delay in their injection. Furthermore, a healthcare professional would not have been able to predict at the time LA CAB plus RPV was started that these 2 individuals were bound for late virologic failure because they did not have 2 or more of the baseline factors associated with CVF in the past. Specifically, they were not obese (ie, they did not have a BMI ≥30 kg/m²) and neither had RPV resistance associated mutations at baseline. One patient did have A6 genotype with L74I polymorphism, but this alone would not have alerted a healthcare professional about the risk of failure. Thus, although failure has been uncommon with LA CAB plus RPV, our ability to predict the rare patient who will fail remains unsatisfactory and the risk seems greater with the Q8W dosing.

Patient Satisfaction With Q8W CAB Plus RPV
The FDA recently approved Q8W dosing of LA CAB plus RPV, further expanding the options to our patients. How will this new option be incorporated into practice? This remains to be seen, but results of the Treatment Satisfaction Questionnaire completed in ATLAS-2M provide good insight into what can be expected. Of note, satisfaction increased from baseline to Week 152 and the improvement favored the Q8W arm at Weeks 24, 48, and 152.

This is consistent with the preference for Q8W dosing in my patients. Compared with Q4W dosing, Q8W dosing will also reduce some of the logistical challenges when transitioning to injectable therapy. What this means is that we will need to combine the science and art of medicine and keep patients at the forefront of decision-making. 

Low Failure Rates
Because overall viral suppression rates with LA CAB plus RPV are very high and durable, I am comfortable presenting both Q4W and Q8W options to my patients. In doing so, I ensure that either option is presented only to those with no history of virologic failure and no known or suspected resistance to RPV or CAB. I make patients aware of the numerically higher number of CVFs with Q8W dosing in the context of very low failure rates overall. Finally, for patients who choose Q8W dosing, I would ask them to consider HIV-1 RNA testing every 4 months, aligned with their visit for injections, at least in the initial years. If asked what evidence I have to support this last consideration, I would admit I have none, but point to the art of medicine and the need for better understanding of the predictors of failure with resistance in patients receiving injectable LA CAB plus RPV.

Your Thoughts?
How do you anticipate incorporating the Q8W LA CAB plus RPV into your clinical practice? Join the discussion by posting a comment.