Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response In HIV Reservoir

Study Overview
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Brief Summary
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A longitudinal observational study in HIV-infected subjects receiving cART addressed to explore the effect of the Tat protein and anti-Tat immunity on the formation and maintenance of HIV-1 virus reservoir.

Detailed Description
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The study is designed as a longitudinal observational study addressed to identify the effects of Tat protein and humoral/cellular anti-Tat immune responses (induced in the natural infection or by Tat vaccination) in HIV-1 reservoir dynamics in blood of HIV infected patients receiving cART. HIV DNA data will be used for analyzing the decay dynamics. The primary objective of the study is to determine the rate of decay of total HIV DNA in blood of anti-Tat antibody (Ab) positive versus anti-Tat Ab negative HIV patients receiving cART. The secondary objectives of the study are to relate the HIV DNA decay data to: the persistence of anti-Tat humoral responses; biomarkers of HIV reservoir stability potentially affected by the Tat protein or anti-Tat immune responses, including: i) apoptotic/survival index of CD4+ T cells; ii) reactivation dynamics of latent HIV in resting CD4+ T cells upon exposure to Tat protein and/or activation stimuli; iii) cellular and humoral biomarkers relevant to inflammation and immune dysregulation.

Official Title
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Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response in Peripheral Blood HIV Reservoir Dynamics

Conditions
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HIV/AIDS

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Diagnosis of HIV-1 infection To be under cART treatment CD4+ T-cell count ≥250 cells/microliters Testing for anti-Tat Ab performed during pre-screening Signed informed consent Exclusion Criteria: 1. Current therapy with immunomodulators or immunosuppressive drugs or chemotherapy for neoplastic disorders.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| anti-Tat Ab positive subjects<br> | Other: No intervention<br>* No intervention<br>|
| anti-Tat Ab negative subjects<br> | Other: No intervention<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV proviral DNA levels | Changes of total HIV-1 proviral DNA copies/1.000.000 CD4+ T-cells | Baseline and through study completion, an average of 3 years | 
| HIV plasma viremia | Changes of HIV plasma viral load (copies/mL) | Baseline and through study completion, an average of 3 years | 
| CD4+ and CD8+ T-cell levels | Changes of CD4+ and CD8+ T-cell counts (cells/microL) | Baseline and through study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lymphocytes subset apoptosis | Apoptotic index of isolated lymphocytes subsets | Baseline and through study completion, an average of 3 years | 
| Induction of replication of competent latent HIV-1 from resting CD4+ T-cell | Quantification of replication competent latent HIV-1 from isolated resting CD4+ T cells [TZM-bl cell based assay (TZA)] | Baseline and through study completion, an average of 3 years | 
| Inflammation/immune activation biomarkers | Plasma levels of inflammation and immune activation biomarkers | Baseline and through study completion, an average of 3 years | 
| Anti-Tat Ab isotypes | Anti-Tat humoral response in terms of anti-Tat IgM, IgG and IgA Ab | Baseline and through study completion, an average of 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tat, HIV/AIDS, Immune responses, HIV reservoire, Biomarkers