Clinical trial NCT06842706: Prevalence of Drug-resistant Hiv-1 Strains in Patients Experiencing Virologic Failure. (MULTIVIR2025)
Official title: Prevalence of Drug-resistant Hiv-1 Strains in Patients Experiencing Virologic Failure.(MULTIVIR2025)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: HIV Infection
Keywords: HIV
drug resistance
antiretrovirals
multi-drug resistant
virological failure
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2025-02-24
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Population of people living with HIV (PLHIV) in virological failure, the proportion of participants with virus resistant or possibly resistant to at least one antiretroviral agent from 4 different therapeutic classes: nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse trancriptase inhibitor (NNRTI), protease inhibitor (PI) and integrase inhibitor (INSTI).

Brief summary: In this cross-sectional, national and multicenter study, the main objective is to determine the prevalence of multi-drug resistant viruses (i.e., viruses that are resistant or possibly resistant to at least one antiretroviral drug from four different therapeutic classes: NRTI, NNRTI, PI, INSTI) among people with HIV 1 (PWH) experiencing virological failure.

Detailed description: Detailed Description:

This is a cross-sectional, national and multicenter study with retrospective and prospective data collection. The study will be conducted in all French virology laboratories that participated in the last quality control for HIV genotypic resistance testing conducted by the ANRS MIE network (n = 42).

Study population All patients treated with antiretrovirals and experiencing virological failure (defined as two consecutive viral loads, at least two weeks apart, greater than 50 copies/mL) can be included in this study.

The study will run for twelve months, with a planned start in 2025. During six months, virologists will be asked to identify all patients meeting the inclusion criteria until they reach 20 patients (for centers following less than 2000 PLWHA) or 40 patients (for centers following more than 2000 PLWHA). Genotypic resistance testing will be performed for all these patients, as recommended by French guidelines. Genotypic resistance testing will always include the amplification of the reverse transcriptase (RT), protease (PR) and integrase (INT), whereas the amplification of gp120, gp41 and/or capsid will only be performed in patients receiving maraviroc, enfuvirtide or lenacapavir, respectively.

Genotypic resistance testing will be performed in each local laboratory, using Sanger or high-throughput sequencing.

Sample size It is estimated that the proportion of patients with multi-drug resistant viruses is between 1 and 5% in this population. Thus, the aim is to include at least 500 patients, which would allow to determine the proportion of multi-drug resistant viruses with an accuracy of 1 to 2%.

With at least 30 participating centers, an expected number of 800 patients should be included. Given the threshold used to define virological failure (50 copies/mL), it is expected that genotypic resistance testing will not be successful in a number of cases. Assuming that all patients with virological failure have viral loads between 51 and 200 copies/mL, and that the success rate for genotypic resistance testing is 63%, the number of patients for whom we would have genotypic data would be 504.

Data collection The virology laboratories will send the list of eligible patients to the associated clinical centers, according to their usual data transfer procedure, so that clinicians can inform the participants and obtain their informed consent. An information form will also be distributed to participants.

A unique identification code will be assigned to each patient that have agreed to this study. An electronic case report form will be used to collect genotypic, clinical and demographic data.

Data analysis Identification of drug resistance-associated mutations will be performed using two different algorithms: Stanford HIVDB (version 9.7, November 2024) and HIV French Resistance (version 35, April 2024).

Eligibility criteria: Inclusion Criteria:

* Patient (male or female) 18 years of age or older.
* Patient who has given his or her consent to participate in the study.
* Patient on antiretroviral therapy for at least six months, with a plasma viral load (VL) greater than 50 copies/mL on at least two consecutive measurements.

Exclusion Criteria:

* Patients opposed to the use of their data.

Primary outcomes:
measure: Drug resistance-associated mutations are those defined in the current ANRS algorithm (https://hivfrenchresistance.org/hiv-french-resitance-tables-of-rules/) and in the current Stanford algorithm (http://hivdb.stanford.edu) at the time of analysis.
timeFrame: Recruitment period: 6 months ·Participation period per participant: 1 day (no follow-up visit) ·Total research period: 12 months · Provisional start date: April 1, 2025 · Provisional end da
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Bichat-Claude Bernard University Hospital, Paris, AP-HP.Nord
name: Quentin Le Hingrat, DR
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Virologie Hôpital Saint-Louis, AP-HP.Nord 1 avenue Claude Vellefaux, 75010 Paris
name: Constance Delaugerre, PR
role: PRINCIPAL_INVESTIGATOR
References: