Cabotegravir Plus Rilpivirine Long-acting Regimen in the Swiss HIV Cohort Study:Uptake, Outcome, and Risk Factors for Treatment Failures

Cabotegravir Plus Rilpivirine Long-acting Regimen in the Swiss HIV Cohort Study: Uptake, Outcome, and Risk Factors for Treatment Failures in a Real-world Setting

This study aims to characterize Swiss HIV Cohort Study participants initiating the CAB+RPV LA regimen, assess adherence to Swiss label indications, and describe treatment outcomes in this large, multicentre, heterogeneous, high-income setting. Moreover, the study aims to assess virological, immunological, demographic, clinical, and behavioural factors associated with viral failure under CAB+RPV LA regimen.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: VOCABRIA 30Mg Tablet; Drug: EDURANT 25Mg Tablet; Drug: Cabotegravir Injectable Suspension; Drug: Rilpivirine Injectable Suspension; Biological: Intact proviral DNA assay; Biological: Full-length sequencing

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Dominique L Braun, MD; Phone Number: 0041442559196; Email: dominique.braun@usz.ch
• Study Contact Backup: Name: Jessy J Duran Ramirez, MSc; Phone Number: 00410446341911; Email: jessy.duranramirez@usz.ch

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • Recruiting
    • University Hospital Zurich
    • Contact: Dominique L Braun, MD; Phone Number: 0041442559196; Email: dominique.braun@usz.ch
    • Contact: Jessy J Duran Ramirez, MSc; Phone Number: 0041446341911; Email: jessy.duranramirez@usz.ch
    • Principal Investigator: Jessy J Duran Ramirez, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of SHCS participants initiating the CAB+RPV LA regimen and a matched control population on a SOC oral regimen (including dual drug regimens)

Description

Inclusion Criteria:

• Participant in the SHCS
• All SHCS participants initiating the CAB+RPV LA regimen
• All SHCS participants on SOC oral regimen

Exclusion Criteria:

• Not participating in the SHCS

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Swiss HIV Cohort Study participants on CAB+RPV LA regimen; Swiss HIV Cohort Study participants initiating the CAB+RPV LA regimen	Drug: VOCABRIA 30Mg Tablet; CAB 30 mg Film-coated tablets; Other Names: Cabotegravir Tablets; Drug: EDURANT 25Mg Tablet; RPV 25 mg film-coated tablets; Other Names: Rilpivirine Tablets; Drug: Cabotegravir Injectable Suspension; CAB LA 600 mg prolonged release suspension for injection (3 mL); Other Names: Vocabria; Drug: Rilpivirine Injectable Suspension; RPV LA 900 mg prolonged release suspension for injection (3 mL); Other Names: Rekambys; Biological: Intact proviral DNA assay; HIV-1 latent reservoir size; Biological: Full-length sequencing; Proviral DNA
Swiss HIV Cohort Study participants on a standard of care oral regimen; Matched control population on a standard of care oral regimen	Biological: Intact proviral DNA assay; HIV-1 latent reservoir size; Biological: Full-length sequencing; Proviral DNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of individuals with viral blips	Proportion of individuals with viral blips (defined as one HIV-1 RNA >50 and <400 c/mL with a next HIV-1 RNA <50 copies/ml)	Month 24
Proportion of individuals with confirmed viral failures	Proportion of individuals with confirmed viral failures (defined as two consecutive HIV-1 RNA ≥ 50 c/mL)	Month 24
Proportion of individuals switching off CAB+RPV LA to previous or another oral regimen	Proportion of individuals switching off CAB+RPV LA to previous or another oral regimen after HIV-1 RNA levels of >50 to <400 copies/mL and >400 copies/mL	Month 24
Time to viral failure	Overall time to confirmed viral failures (defined as two consecutive HIV-1 RNA ≥ 50 c/mL)	Up to month 24
Proportion of participants who discontinue treatment due to drug-related reasons	Proportion of participants who discontinue treatment due drug-related reasons and re-suppression regimens (such as adverse events, confirmed viral failure, low level viremia or low blood concentration measurements) including the choice of re-suppression regimens.	Month 24
Proportion of participants who discontinue treatment due to drug-unrelated reasons	Proportion of participants who discontinue treatment due drug-unrelated reasons and re-suppression regimens (such as patient wish, death, migration, and loss to follow-up) including the choice of re-suppression regimens.	Month 24
Proportion of participants by characteristics	- Proportion of participants by socio-demographic and clinical characteristic(s) (e.g., by age, sex, body mass index, race, geographic origin, education, transmission mode, HIV-1 RNA levels, CD4 cell count, duration of HIV-1 infection, HIV-1 subtype, previous regimen, genotypic resistance profile, coinfections, lifestyle variables, and co-medications)	Month 24
Overall adherence to Swiss label indication in CAB+RPV LA prescriptions	- Overall adherence to Swiss label indication in CAB+RPV LA prescriptions between care providers, such as university hospital versus private physicians, and among nationwide centres	Month 24
Overall adherence to the proposed injection schedules	- Overall adherence to the proposed injection schedules quantified by deriving an CAB+RPV LA adherence threshold (e.g., accounting for any missed injection, daily oral bridging ART, and delayed injection of +7 days according to the Swiss label indication)	Month 24
Proportion of participants by treatment adherence category	- Proportion of participants by treatment adherence categories (e.g., optimal, sub-optimal, and poor adherence)	Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate in-depth factors associated with viral blips and viral failure	Proportion of individuals by risk factor(s) (e.g., by body mass index, race, geographic origin, education, HIV-1 RNA levels, CD4 cell count, duration of HIV-1 infection, HIV-1 subtype, previous regimen, treatment adherence, CAB+RPV LA plasma concentrations measured at time of failure, genotypic resistance profile , lifestyle variables, and co-medications)	Month 24
Measure intact proviral DNA as potential predictor for viral failure	Measure intact proviral DNA as potential predictor for viral failure among PWH initiating CAB+RPV LA regimen and compare with the matched control population on a SOC oral regimen	Month 24
Assessment of resistance associated mutations from proviral DNA as potential predictor for viral failure	Assessment of resistance associated mutations from proviral DNA as potential predictor for viral failure among PWH initiating CAB+RPV LA regimen and compare with the matched control population on a SOC oral regimen	Month 24

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Swiss HIV Cohort Study
• Investigators: Principal Investigator: Jessy J Duran Ramirez, MSc, Department of Infectious Diseases and Hospital epidemiology, University Hospital Zürich

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 15, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Rilpivirine; Cabotegravir
• Other Study ID Numbers: 903_SHCS; 222485 (Other Grant/Funding Number: ViiV Healthcare)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No