Comparison of Inflammatory Markers and Incidence of Comorbidities in Patients on Antiretroviral Therapy With Second-generation Anti-integrase Drugs on Triple Versus Dual Therapy (COLLATERAL 2)

Comparison of Inflammatory Markers and Incidence of Comorbidities in Patients on Antiretroviral Therapy (ART) With Second-generation Anti-integrase Drugs on Triple Versus Dual Therapy

HIV-infected patients develop comorbidities earlier than the general population. Immune activation with the secretion of pro-inflammatory cytokines would play a major role in the occurrence of these comorbidities. Numerous factors, called risk factors, already identified in the general population and confirmed in patients with HIV virus favor the occurrence of these comorbidities but cannot alone explain the overrepresentation and precocity of these comorbidities in the HIV population. Investigators hypothesize that optimization or simplification with certain classes of antiretrovirals modify the inflammatory response and are predictive factors for the occurrence of comorbidities

Study Overview

• Status: Recruiting
• Conditions: Hiv
• Intervention / Treatment: Other: plasma inflammatory markers; Other: CD4/CD8 ratio

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jacques Durant; Phone Number: +33 04.92.03.97.11; Email: durant.j@chu-nice.fr

Study Locations

• France
  • Cannes, France, 06614
    • Recruiting
    • CH Simone VEIL
    • Contact: Matteo VASSALLO; Phone Number: 04 92 18 67 08; Email: M.VASSALLO@ch-cannes.fr
  • Nice, France
    • Recruiting
    • CHU Nice
    • Contact: Jacques Durant; Phone Number: +33 04.92.03.97.11; Email: durant.j@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HIV-1 infection
• Age > 40 years or adults with more than 10 years of antiretroviral therapy
• Switching to BIC/FTC/TAF or DTG/3TC or DTG+3TC within the last 2 years
• Plasma HIV-1 RNA viral load < 50 copies/ml for more than 6 months
• Absence of chronic hepatitis B infection
• Absence of genotype mutations on Dolutegravir (DTG) or Bictegravir (BIC) or tenofovir alafenamide TAF
• Daily use of antiretroviral therapy
• Effective contraception for women of childbearing potential will be requested
• Signed informed consent
• Enrollment in a Social Security plan

Exclusion Criteria:

• Non-daily or intermittent antiretroviral therapy regimen (e.g., 4 or 5 days a week)
• Pregnancy or breastfeeding
• Vulnerable persons according to article L.1121-6 of the public health code Persons unable to give consent according to article L.1121-8 of the public health code
• Opportunistic infections during curative treatment
• HIV-2 infection
• Active hepatitis C
• Refusal to participate
• Withdrawal of informed consent by the patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patients on antiretroviral therapy with second generation anti-integrase drugs in triple therapy	Other: plasma inflammatory markers; Evolution of different plasma inflammatory markers (CRP, IL6, D-Dimers, CD14s, CD163, IL-1, IP-10, MCP-1, IL-18, IFAB); Other: CD4/CD8 ratio; Evolution of CD4/CD8 ratio
Experimental: patients on antiretroviral therapy with second generation anti-integrase drugs in dual therapy	Other: plasma inflammatory markers; Evolution of different plasma inflammatory markers (CRP, IL6, D-Dimers, CD14s, CD163, IL-1, IP-10, MCP-1, IL-18, IFAB); Other: CD4/CD8 ratio; Evolution of CD4/CD8 ratio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma inflammatory markers	To measure the evolution of different plasma inflammatory markers (CRP, IL6, D-Dimers, CD14s, CD163, IL-1, IP-10, MCP-1, IL-18, IFAB) over 3 years between the 2 groups.	3 years after baseline
CD4/CD8 ratio	To measure the evolution of CD4/CD8 ratio over 3 years between the 2 groups. A CD4/CD8 ratio is considered normal if it is greater than 0.75. Immune hyperactivation occurs when the ratio is below 0.75	3 years after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological failure rate (year 1)	Virological failure rate (plasma HIV-1 RNA viral load > 50 copies/ml on two consecutive measurements)	One year after baseline
residual viremia rate (year 1)	Evolution of the residual viremia rate (detected or quantifiable plasma HIV-1 RNA viral load < 50 copies/ml)	One year after baseline
Virological failure rate (year 2)	Virological failure rate (plasma HIV-1 RNA viral load > 50 copies/ml on two consecutive measurements)	two years after baseline
Residual viremia rate (year 2)	Evolution of the residual viremia rate (detected or quantifiable plasma HIV-1 RNA viral load < 50 copies/ml)	two years after baseline
Virological failure rate (year 3)	Virological failure rate (plasma HIV-1 RNA viral load > 50 copies/ml on two consecutive measurements)	three years after baseline
Residuak viremia rate (year 3)	Evolution of the residual viremia rate (detected or quantifiable plasma HIV-1 RNA viral load < 50 copies/ml)	3 years after baseline
Prevalence of neuropsychiatric events at 1 year	To analyze the evolution at 1 year of the prevalence of neuropsychiatric events (including sleep disorders, anxiety, depression) between the two groups from the questionnaires.	1 year after baseline
Prevalence of neuropsychiatric events at 2 years	To analyze the evolution at 2 years of the prevalence of neuropsychiatric events (including sleep disorders, anxiety, depression) between the two groups from the questionnaires.	2 years after baseline
Prevalence of neuropsychiatric events at 3 years	To analyze the evolution at 2 years of the prevalence of neuropsychiatric events (including sleep disorders, anxiety, depression) between the two groups from the questionnaires.	3 years after baseline
changes in antiretroviral therapy (year 1)	Analyze the 1-year change in the prevalence of changes in antiretroviral therapy and the reasons for changes between the two groups based on questionnaires	1 year after baseline
changes in antiretroviral therapy (year 2)	Analyze the 2-years change in the prevalence of changes in antiretroviral therapy and the reasons for changes between the two groups based on questionnaires	2 years after baseline
changes in antiretroviral therapy (year 3)	Analyze the 3-years change in the prevalence of changes in antiretroviral therapy and the reasons for changes between the two groups based on questionnaires	3 years after baseline
Evolution of intracellular markers (CD8/CD38, HLA-DR) (year 1)	To analyze the evolution of intracellular markers (CD8/CD38, HLA-DR) at 1 year between the two cohorts in high-risk subjects (nadir CD4<200 cells/mm3 or history of AIDS stage, or subject aged ≥ 65 years)	1 year after baseline
plasma markers assay (year 1)	Analyze the evolution of plasma markers at 1 year between the two cohorts in high-risk subjects (nadir CD4<200 cells/mm3 or history of AIDS stage, or subject aged ≥ 65 years)	1 year after baseline
plasma markers assay (year 2)	Analyze the evolution of plasma markers at 2 years between the two cohorts in high-risk subjects (nadir CD4<200 cells/mm3 or history of AIDS stage, or subject aged ≥ 65 years)	2 years after baseline
plasma markers assay (year 3)	Analyze the evolution of plasma markers at 3 years between the two cohorts in high-risk subjects (nadir CD4<200 cells/mm3 or history of AIDS stage, or subject aged ≥ 65 years)	3 years after baseline
risk factors for immune hyper activation	Analyze and compare risk factors for immune hyper activation (age, CD4 nadir<200 cells/mm3, AIDS stage, residual viremia, archived M184V/I resistance...) in each group	3 years after baseline
immune activation markers assays and identification of comorbidities	Correlate immune activation markers with the occurrence of comorbidities	3 years after baseline
comorbidities (year 1)	Measurement of the true incidence of major 11 comorbidities (Depression, Cardiovascular, Osteoporosis, Non-AIDS related cancers, Metabolic syndrome, Cognitive disorders, Chronic renal failure , proximal renal tubulopathy, Hepatic fibrosis, Chronic Obstructive Pulmonary Disease, Osteoarthritis) at 1 year	1 year after baseline
comorbidities (year 2)	Measurement of the true incidence of major 11 comorbidities (Depression, Cardiovascular, Osteoporosis, Non-AIDS related cancers, Metabolic syndrome, Cognitive disorders, Chronic renal failure , proximal renal tubulopathy, Hepatic fibrosis, Chronic Obstructive Pulmonary Disease, Osteoarthritis) at 2 years	2 years after baseline
comorbidities (year 3)	Measurement of the true incidence of major 11 comorbidities (Depression, Cardiovascular, Osteoporosis, Non-AIDS related cancers, Metabolic syndrome, Cognitive disorders, Chronic renal failure , proximal renal tubulopathy, Hepatic fibrosis, Chronic Obstructive Pulmonary Disease, Osteoarthritis) at 3 years	3 years after baseline
Onset of new comorbidity	Measure the time to onset of new comorbidity(ies) in each group.	3 years after baseline
patient profiles	Describe patient profiles at risk for comorbidities based on different inflammatory biomarkers	3 years after baseline
individualized and computerized care plan	Establish an individualized and computerized care plan for the patient after evaluation of the risk factors (according to the profiles) to detect the occurrence or aggravation of comorbidities	3 years after baseline

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Jacques Durant, durant.j@chu-nice.fr

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2023
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: December 27, 2022
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 22-PP-04

Drug and device information, study documents

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