A Global Registry on Second GEneration and Long-acting InTegrase InhibiTor FAilures (ROSETTA)

ROSETTA- a Global Registry on Second GEneration and Long-acting InTegrase InhibiTor FAilures

Integrase strand transfer inhibitors (INSTI) inhibit HIV replication by preventing the integration of viral HIV DNA into the host's genome. INSTIs are used as part of combination antiretroviral therapy (cART) regimens for both treatment-naive and treatment experienced patients.

In clinical practice, virological failure to second generation INSTIs is rare and often without selection of known resistance mutations. Considering the use of INSTIs in first line regimens in high income countries and the increasing roll-out in lower and middle income countries, a better understanding of relevant resistance development and clinical failure is urgently needed.

The ROSETTA registry aims at systematically collecting otherwise scattered information on individual cases failing second generation integrase inhibitors, with the goal to inform policy and future use of INSTIs in the treatment of people living with HIV.

Attending physicians of individuals who are experiencing virological failure on a second generation integrase inhibitor-containing regimen are invited to contribute data to the registry.

Study Overview

• Status: Enrolling by invitation
• Conditions: HIV; Therapy Failure

Detailed Description

The ROSETTA study collects clinical data and HIV sequences from individuals experiencing failure of ART containing second generation INSTIs from Americas, Africa and Europe. If resistance testing is not available, the ROSETTA team can perform genotypic resistance testing of RT, protease, integrase and 3'-PPT.

Research objectives:

To set up a database with data of individuals who have experienced virological failure on a regimen containing a second generation INSTI To determine the prevalence of resistance mutations in integrase and 3'-PPT in the dataset To identify possible new resistance mutations outside integrase and 3'-PPT. providing additional funding is retrieved.

The study design will be a multicenter observational cohort study. Patients will be included from HIV care centers in Europe, America and Africa, if they fullfill the inclusion criteria.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

People living with HIV-1 experiencing virological failure to second-generation integrase inhibitors from Africa, Americas and Europe.

Description

Inclusion Criteria:

• Confirmed HIV-1 infection
• Using cART (any regimen) for at least the last 6 months
• Experiencing virological failure* on a second generation INSTI-containing regimen (including monotherapy and dual-therapy regimens)
• Data on current regimen and previous INSTI exposure available (start/stop dates and dosing mandatory)
• Integrase genotypic data available (performed locally) or a plasma/DBS (or CSF if available) sample(s) drawn at time of failure available to perform genotypic testing centrally * Virological failure is defined as at least 2 consecutive viral loads (VL) above 50 copies/mL in plasma or 1 VL above 200 copies/mL in plasma. We will also include patients who have a VL of >50 copies/mL in CSF, independent of the VL in plasma.

Exclusion Criteria:

• Submitted fasta file not passing quality control and unavailability of a stored sample to repeat sequence analysis
• Missing Mandatory data
• Documented treatment interruption for at least 2 weeks prior to viral load testing.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence and patterns of resistance in the dataset	The prevalence of resistance in the dataset in relation to HIV subtype and collected clinical parameters	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Identify new mutations related to integrase inhibitor resistance	3 years

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Erasmus Medical Center; Luxembourg Institute of Health
• Investigators: Principal Investigator: Annemarie MJ Wensing, MD,PhD, UMC Utrecht

Publications and helpful links

General Publications

• Special Issue: Abstract Supplement HIV Glasgow 10-13 November 2024, Glasgow, UK/Virtual. J Int AIDS Soc. 2024 Nov;27 Suppl 6:e26370. doi: 10.1002/jia2.26370. No abstract available.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): September 1, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Estimated): November 27, 2024

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: HIV drug resistance; integrase inhibitors; subtype
• Other Study ID Numbers: V0002187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: ROSETTA will not own the data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No