ABSTRACT
Background. Cabotegravir + Rilpivirine Long Acting (CAB+RPV LA) every 2 months is a recommended regimen in European and US treatment guidelines for PLWH with virological suppression and no known resistance to CAB or RPV. CARISEL, an implementation study, is the first study where all participants switched from standard oral therapy to 2 monthly CAB+RPV. Key clinical and implementation secondary endpoints are reported. Methods. This single arm study enrolled virologically-suppressed PLWH to receive CAB+RPV LA 2-monthly at 18 clinics in 5 EU countries, conducted from Sept 2020-Feb 2022. Clinics with no prior experience with CAB+RPV LA were preferentially selected. Sites were randomized to standard implementation (Arm-S) or enhanced implementation (Arm-E) which included additional implementation strategies. Proportion of participants with plasma HIV-1 RNA >=50c/mL and < 50c/mL at Month 12 (FDA Snapshot algorithm, ITT-E) were reported. Adverse events, COVID-related events, clinic visit length, and safety were analyzed by implementation arm. Results. 72% of clinics (13/18) had no experience with CAB+RPV LA at study start. 430 enrolled and treated participants were included with 25% female, 18% black, and a mean baseline age of 44 yrs (30% > 50 years). At Month 12, 87% of participants maintained virologic suppression in each implementation arm (Table 1) and 1 participant (1/430;0.23%) in Arm-E experienced confirmed virologic failure. Grade 1-2 AEs were reported in Arm-E:99% vs Arm-S: 97%;Grade 3-4 drug-related AEs reported in Arm-E: 4%, Arm-S: 8%. ISRs were reported in 86% of participants;98% were mild or moderate, median duration of 3 days and a low proportion of participants discontinued treatment due to ISR (6%). Total time in clinic decreased more in Arm-E than Arm-S;visit length varied by country (Table 2). COVID was diagnosed in 16% of participants. COVID-19 related protocol deviations reported in 3% of participants. There were no discontinuations and no snapshot failures due to COVID-19. Conclusion. Regardless of implementation arm, CAB+RPV LA was a highly effective and well tolerated, consistent with clinical outcomes in the Phase 3 clinical program. Clinic visit lengths varied by country and decreased over time. COVID-19 did not lead to treatment disruption or study discontinuation. (Table Presented).
ABSTRACT
Background: Dolutegravir/Lamivudine (DTG/3TC) 2-drug regimen (2DR) was non-inferior to a tenofovir alafenamide (TAF)-based 3-/ 4-drug regimen (3/4DR) (TBR) through the Week 48 primary endpoint in TANGO. Here we present prespecified Week 96 secondary analyses from TANGO. Method: TANGO, a randomized, open-label, non-inferiority phase III study, evaluates efficacy and safety of switching to once-daily DTG/3TC in HIV-1- infected, virologically suppressed adults vs remaining on a TBR over 148 weeks. Week 96 analysis assessed non-inferiority with a 4% non-inferiority margin for Snapshot virologic failure (VF) and 8% for virologic success (VS;US Food and Drug Administration Snapshot algorithm, intention-to- treat- exposed [ITT-E] population). Results: 741 participants were randomized/exposed (DTG/3TC: 369;TBR: 372). For Snapshot VF, switching to DTG/3TC was non-inferior to continuing TBR at Week 96 in the ITT-E analysis: 0.3% vs 1.1%;adjusted difference: -0.8% (95% CI: -2.0, 0.4) and superior to TBR in the per-protocol analysis: 0% vs 1.1%;adjusted difference: -1.1% (95% CI: -2.3, -0.0);P = 0.044 (2-sided). Snapshot VS was high in both arms (DTG/3TC: 85.9%;TBR: 79.0%;adjusted difference: 6.8% [95% CI: 1.4-12.3]). Forty-four participants (5.9%) had missing data in the Week 96 window due to COVID-19. No participants on DTG/3TC and 3 (<1%) on TBR met confirmed virologic withdrawal (CVW) criteria, with no resistance observed at failure. Overall adverse event (AE) rates were similar between arms, with more drug-related AEs in the DTG/3TC arm. Total cholesterol (TC), low-density lipoprotein cholesterol, and triglycerides improved significantly with DTG/3TC, whereas high-density lipoprotein (HDL) cholesterol changes significantly favored TBR, with no difference in TC/HDL-cholesterol ratio between arms. Decreases in glomerular filtration rate by cystatin C were observed with significantly lower decreases in the DTG/3TC arm;proximal tubular function marker changes were small and similar across arms. Conclusion: At Week 96, switching to DTG/3TC FDC was non-inferior to continuing a TAF-based 3/4DR in maintaining virologic suppression in HIV-1- infected antiretroviral therapy-experienced adults. The safety profile of DTG/3TC FDC was consistent with the DTG and 3TC respective labels. DTG/3TC 2DR offers a robust switch option with durable efficacy, good safety and tolerability, and a high barrier to resistance with zero CVWs through 96 weeks.