Long-Acting Cabotegravir and Rilpivirine for HIV-1 Suppression

Switch to 2-Monthly Dosing After 5 Years of Daily Oral Therapy

Anthony Mills; Gary J. Richmond; Cheryl Newman; Olayemi Osiyemi; Jerry Cade; Cynthia Brinson; Jerome De Vente; David A. Margolis; Kenneth C. Sutton; Viviana Wilches; Sarah Hatch; Jeremy Roberts; Cynthia McCoig; Cindy Garris; Kati Vandermeulen; William R. Spreen

Disclosures

AIDS. 2022;36(2):195-203. 

In This Article

Discussion

The results from the POLAR study complement those collected from larger Phase 3 studies and together support the therapeutic potential of i.m. CAB+RPV long-acting administered monthly or Q2M for the maintenance of virologic suppression in PWH.[17–19] Notably, the POLAR study is the first clinical study to investigate the CAB+RPV long-acting regimen dosed Q2M, as indicated, instead of every 8 weeks.

The high level of virologic suppression and low rate of CVF reflect the results obtained from the larger Phase 3 studies of CAB+RPV long-acting, and contribute to a growing library of clinical evidence supporting its efficacy as a maintenance regimen.[17–19] Furthermore, the safety and tolerability profile was consistent with previous studies and no new safety signals were identified.[17–19] As previously observed, ISRs were of mild-to-moderate intensity, of short duration, and decreased in incidence over time.[17–19] Notably, ISRs did not lead to treatment discontinuation.

Participants transitioning from the Phase 2b LATTE study were treatment experienced, having received daily oral CAB+RPV for at least 5 years. At the beginning of the Maintenance Phase, 93% (n = 90/97) of study participants elected to receive CAB+RPV long-acting over daily oral tablets. This may reflect the substantial interest in long-acting therapies observed in the population of PWH and serves as an encouraging sign for the clinical uptake of the injectable regimen.[24–28] Notably, participants were more satisfied with the regimens that they chose to receive in POLAR (both CAB+RPV long-acting and oral DTG/RPV) than with the daily oral CAB+RPV regimen they had previously received for at least 5 years, as measured by the HIVTSQc. In addition, 88% (n = 77/88) of CAB+RPV long-acting respondents stated a preference for CAB+RPV long-acting over their prior oral regimen, consistent with findings from the other Phase 3 studies (ATLAS, FLAIR, and ATLAS-2 M) evaluating CAB+RPV long-acting.[17–19,29–31] Taken together, these results demonstrate high levels of preference for, and satisfaction with, the injectable regimen.

Limitations

Owing to the small number of participants enrolled, the study was not adequately powered to draw statistical inferences from the results. Further, as participants could choose which maintenance regimen they received, POLAR was nonrandomized and, therefore, the numbers of participants differed greatly between comparator arms. As a result, comparisons between CAB+RPV long-acting and DTG/RPV cannot be drawn and any differences in results must be interpreted within this context. In addition, all participants had completed more than 300 weeks of oral CAB+RPV therapy prior to study entry and are therefore a highly selected population comprising participants with established efficacy with, and tolerability to, CAB+RPV. This caveat limits the generalizability of the findings to a wider population initiating CAB+RPV long-acting as a novel regimen. The small number of females (sex at birth) in the study should also be considered in the interpretation of the findings. The design of the study prevented blinding, which could influence the reporting of adverse events and patient-reported outcomes; however, this would not affect the efficacy findings, which were based on objective measurements of viral load.

Conclusion

Injectable CAB+RPV long-acting, administered Q2M, maintained high levels of virologic suppression in participants previously treated with oral CAB+RPV, with no participants having virologic nonresponse or meeting the CVF criterion through Month 12 of the POLAR study. The injectable CAB+RPV long-acting regimen was well tolerated and preferred over oral therapy by this treatment-experienced cohort, who had previously received daily oral CAB+RPV for at least 5 years in the LATTE study. Taken together, these results complement the results observed in larger Phase 3 studies evaluating the injectable regimen and support CAB+RPV long-acting as an efficacious and well-tolerated Q2M maintenance therapy for PWH.

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