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

Centre Hospitalier Universitaire de Nice500 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

500

Conditions

Hiv

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: 3 years after baseline

Secondary Outcomes

Virological failure rate (year 1)

Virological failure rate (plasma HIV-1 RNA viral load \> 50 copies/ml on two consecutive measurements)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 3 years after baseline

immune activation markers assays and identification of comorbidities

Correlate immune activation markers with the occurrence of comorbidities

Time frame: 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

Time frame: 1 year after baseline

comorbidities (year 2)

Time frame: 2 years after baseline

comorbidities (year 3)

Time frame: 3 years after baseline

Onset of new comorbidity

Measure the time to onset of new comorbidity(ies) in each group.

Time frame: 3 years after baseline

patient profiles

Describe patient profiles at risk for comorbidities based on different inflammatory biomarkers

Time frame: 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

Time frame: 3 years after baseline

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts