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School of Population Medicine
University of New South Wales
Senior Staff Specialist
South Eastern Sydney Local Health Network
Prof. Don Smith has disclosed that he has received funds for research support from ViiV and consulting fees from Gilead Sciences, Janssen, and ViiV.
Although cabotegravir (CAB) plus rilpivirine (RPV) is the only long-acting injectable HIV therapy that has received regulatory approval for use in Australia, there is considerable interest in this broader strategy of injectable agents, as it represents a quantum shift in HIV management in much the same way as long-acting reversible contraception did for reproductive health. Long-acting injectables were a topic that received much attention at the 18th European AIDS Conference (EACS 2021).
Long-Acting Cabotegravir Plus Rilpivirine
Most of the studies presented at EACS 2021 were on the CAB plus RPV combination. Scherzer and colleagues reported a cross-study comparison of the 136 patients receiving CAB plus RPV every 2 months in the ATLAS-2M study with the 283 subjects receiving dolutegravir/lamivudine/abacavir in the FLAIR study. They found no statistically significant differences in efficacy or safety between patient groups in the 2 studies.
Molina and colleagues presented the European phase III/IIIb experience in 48 weeks with 522 patients receiving CAB plus RPV every 4 or every 8 weeks within the ATLAS, FLAIR, and ATLAS-2M studies. Using an intention-to-treat efficacy analysis, they found that 95% of European patients in these studies maintained viral suppression. Only 3 subjects were withdrawn from studies due to confirmed virological failures. Injection site reactions were common (reported in approximately 80% of patients) but fortunately were mostly mild, and the incidence decreased to approximately 20% of patients by Week 48.
In this population willing to enroll into a study where they would receive injectable therapy, most (90%) stated that they preferred injectable to oral therapy. However, for patients who like the appeal of not having to take tablets, the oral lead-in dosing required for CAB plus RPV is a bit off-putting. This brings up the question: Is oral lead-in for CAB plus RPV really needed? To address this, de los Rios and colleagues pooled data from the lead-in dosing of ATLAS, FLAIR, and ATLAS-2M and reviewed safety issues. Overall, only 1 subject withdrew from the study due to an adverse event that was deemed possibly related to the oral lead-in phase and thus was prohibited from proceeding to injectable therapy, suggesting there is little risk in removing the oral lead-in.
Is this injectable stuff all just a bit too difficult to implement? Maybe not. CARISEL is a phase IIIb implementation study across 5 European countries that surveyed healthcare staff at Months 1 and 5 into the project to assess their perceptions of barriers to implementation.
Initial concerns varied by country but centered on the risk of inducing resistance if patients missed doses, having adequate staff available, and patients being unable to attend appointments as scheduled. Similar concerns have been raised by Australian healthcare staff. Each of these concerns lessened by 5 months. Most staff felt positive about the program and that it was best suited to HIV specialist services.
Time spent by patients attending appointments for injections also dropped from an average of 85 minutes to 54 minutes by Month 5 in the enhanced implementation arm, which received face-to-face injection training. These analyses demonstrate that long-acting CAB plus RPV implementation in the outpatient setting was acceptable and feasible.
As noted with the earlier International AIDS Society 2021 conference, a glimpse into the future was seen with the study by Stellbrink and colleagues of a 26-week analysis of the CAPELLA trial. This was an open-label study of the novel capsid-inhibitor lenacapavir, which was given subcutaneously every 6 months to 36 highly treatment experienced subjects. Overall, 81% were able to achieve viral suppression with a mixture of background antiretrovirals. Lenacapavir, a new class of drug with significant potency and suitable for 6 monthly doses, has an exciting future in Australia and around the globe.
What challenges have you encountered with implementing the use of long-acting antiretroviral agents in your practice? Join the discussion by posting a comment. For more details on this and other key HIV issues from EACS 2021, review more CCO Conference Coverage, including capsule summary slide sets, video recaps with expert faculty, and other ClinicalThought commentaries highlighting US and global perspectives.