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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Hiv

Intervention / Treatment
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* Other: plasma inflammatory markers
* Other: CD4/CD8 ratio


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |