Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy

Abstract

Objectives: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2 months (Q2M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809). Design: A Phase 2b, multicenter, open-label, rollover study. Methods: LATTE participants with plasma HIV-1 RNA less than 50 copies/ml who completed at least 300 weeks on study were eligible. Participants elected to switch to either CAB+RPV long-acting Q2M or daily oral dolutegravir/RPV for maintenance of virologic suppression. The primary endpoint was the proportion of participants with HIV-1 RNA greater than or equal to 50 copies/ml at Month 12 (M12) per the Food and Drug Administration Snapshot algorithm. The incidence of confirmed virologic failure (CVF, two consecutive HIV-1 RNA measurements greater than or equal to 200 copies/ml), as well as safety, laboratory, and patient-reported outcomes (HIV Treatment Satisfaction and preference questionnaires) were also assessed. Results: Of 97 participants enrolled, 90 chose to receive CAB+RPV long-acting and seven chose dolutegravir/RPV. At M12, no participant had HIV-1 RNA greater than or equal to 50 copies/ml or met the CVF criterion in either treatment group. No new safety signals were identified. Total treatment satisfaction was high at Baseline and remained stable through M12 across both treatment groups. Overall, 88% ( n = 77/88) of long-acting arm participants preferred CAB+RPV long-acting to oral CAB+RPV. Conclusion: CAB+RPV long-acting maintained virologic suppression in participants who had previously received daily oral CAB+RPV for at least 5 years in LATTE, with a favorable safety profile. Most participants preferred CAB+RPV long-acting to their prior oral CAB+RPV regimen at M12.

Brief Report: Impact of COVID-19 on Cabotegravir Plus Rilpivirine Long-Acting Dosing Across 6 Ongoing Global Phase IIb and III Clinical Trials

“…Participants included were from the LATTE-2 (n = 274; NCT02120352) and POLAR (n = 90; NCT03639311) phase IIb studies, ATLAS (n = 481; NCT02951052) and FLAIR (n = 515; NCT02938520) phase III studies, and ATLAS-2M (n = 1045; NCT03299049) and CUSTOMIZE (n = 115; NCT04001803) phase IIIb studies. 1,3,8–10 Study protocols for each trial are summarized on ClinicalTrials.gov. 11–16 All study protocols were approved by an investigational center ethics committee or institutional review board.…”

“…This analysis assesses implementation fidelity, reasons for COVID-19-impacted visits, and use of oral therapy to maintain continuous ART across 6 phase IIb/III/IIIb cabotegravir + rilpivirine LA clinical trials that were ongoing during the COVID-19 pandemic. 1,3,[8][9][10] Study protocols for each trial are summarized on ClinicalTrials.gov. [11][12][13][14][15][16] All study protocols were approved by an investigational center ethics committee or institutional review board.…”

Antiretroviral Treatment of HIV-2 Infection: Available Drugs, Resistance Pathways, and Promising New Compounds

“…CAB, approved in 2021, is the first long-acting injectable INSTI to be used in combination with RPV as a substitute antiretroviral regimen in HIV-1-infected adult patients who are virologically suppressed [ 135 ]. Two studies have evaluated the activity of CAB against HIV-2 isolates in cell culture.…”

People with HIV pioneers of injectable cabotegravir and rilpivirine long acting in Italy: who are they?

“…Injectable cabotegravir (CAB) and rilpivirine (RPV) became the first approved long-acting regimen for HIV-1 treatment in adults [1], showing long-term efficacy in maintaining HIV-1 suppression and demonstrating noninferiority to oral therapy [2][3][4][5]. This innovating treatment option had shown good tolerability and high treatmentsatisfaction, with reported adverse effect (AE) mainly represented by injection-site reactions (ISR) which in most cases did not lead to treatment discontinuation [6][7][8][9]. Treatment-eligibility criteria were absence of resistanceassociated mutations (RAMs), previous virological failures (VFs) for nonnucleoside reverse transcriptase inhibitors (NNRTI) and/or integrase stand inhibitors (INSTI) and HBV-coinfection [10,11].…”