Clinical trial NCT06706986: A Global Registry on Second GEneration and Long-acting InTegrase InhibiTor FAilures
Official title: ROSETTA- a Global Registry on Second GEneration and Long-acting InTegrase InhibiTor FAilures
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: HIV
Therapy Failure
Keywords: integrase inhibitors
HIV drug resistance
subtype
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Luxembourg Institute of Health
name: Erasmus Medical Center
First posted: 2024-11-27
Enrollment: 250
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Prevalence and patterns of resistance in the dataset
timeFrame: 3 years
Secondary outcomes:
measure: Identify new mutations related to integrase inhibitor resistance
timeFrame: 3 years
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: UMC Utrecht
name: Annemarie MJ Wensing, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Special Issue: Abstract Supplement HIV Glasgow 10-13 November 2024, Glasgow, UK/Virtual. J Int AIDS Soc. 2024 Nov;27 Suppl 6(Suppl 6):e26370. doi: 10.1002/jia2.26370. No abstract available.