Residual Replication of HIV-1 in the Gut Associated Lymphoid Tissue (GALT) of Patients on Highly Active Antiretroviral Therapy (HAART): the ANRS EP 44 Study

Study Overview
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Brief Summary
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HIV-1 cannot be eradicated from infected individuals by current antiretroviral regimens. Cellular reservoirs and tissue sanctuary sites allow latent HIV-1 persistence and ongoing low-level virus replication. This project aims to characterize the residual replication of HIV-1 in subjects on antiretroviral therapy, particularly in the gut-associated lymphoid tissue.

Detailed Description
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Highly active antiretroviral therapy (HAART) successfully controls HIV-1 replication in most individuals, resulting in substantial immune restoration and decreased morbidity and mortality. However HIV-1 cannot be eradicated from infected individuals by current regimens. Cellular reservoirs and tissue sanctuary sites allow latent HIV-1 persistence and ongoing low-level virus replication, despite maximum virus suppression on HAART. This project aims to characterize the residual replication of HIV-1 in subjects on HAART, particularly in the gut-associated lymphoid tissue (GALT). A group of 20 HIV-1-infected patients on effective HAART will undergo GI endoscopy and GALT biopsies will be taken. A sample of venous blood will also be collected. These samples will be use to characterize the residual viral populations on effective HAART in three compartments, plasma, monocytes, and GALT. HIV-1 coreceptor usage and its evolution on HAART will be characterized in virus reservoirs. This project could provide further insights into the residual replication of HIV-1 in subjects receiving HAART.

Official Title
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Characterization of the Residual Replication of HIV-1 in the Gut-associated Lymphoid Tissue in Patients Receiving Effective Highly Active Antiretroviral Therapy: the ANRS EP 44 Study

Conditions
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HIV Infection

Intervention / Treatment
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* Procedure: GI endoscopy and GALT biopsies
* Biological: A sample of venous blood will also be collected


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infection (ELISA and western-blot tests) Continuous antiretroviral therapy >= 12 months Plasma HIV-1 RNA =< 40 copies/ml >= 6 months Indication of gastro-intestinal endoscopy Age >= 18-year old Physical examination Informed consent Exclusion Criteria: Plasma HIV-1 RNA > 40 copies/ml in the last 6 months Involvement in a HIV vaccine study Treatment with interferon-alpha or PEG- interferon-alpha in the last 6 months Treatment with interleukin-2 in the last 6 months Decompensated cirrhosis Abnormal hemostasis tests Inflammatory bowel disease ; coeliac disease Lymphoma Blood transfusion in the last 6 months Absence of social security (health insurance) Pregnant or breastfeeding woman Incapable adult

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HIV-1-infected patients on effective HAART<br> | Procedure: GI endoscopy and GALT biopsies<br>* This project aims to characterize the residual replication of HIV-1 in subjects on HAART, particularly in the gut-associated lymphoid tissue (GALT)<br>Biological: A sample of venous blood will also be collected<br>* These samples of blood will be use to characterize the residual viral populations on effective HAART in three compartments, plasma, monocytes, and GALT<br>|
| Other: Non Infected HIV Volunteers<br> | Procedure: GI endoscopy and GALT biopsies<br>* This project aims to characterize the residual replication of HIV-1 in subjects on HAART, particularly in the gut-associated lymphoid tissue (GALT)<br>Biological: A sample of venous blood will also be collected<br>* These samples of blood will be use to characterize the residual viral populations on effective HAART in three compartments, plasma, monocytes, and GALT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between HIV-1 viral load and CD4+ T lymphopenia in the GALT. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 DNA load in the GALT vs blood CD4+ T cells |  |  | 
| HIV-1 tropism in the GALT vs blood CD4+ T cells |  |  | 
| Characterization of residual HIV-1 in the plasma < 40 copies/ml |  |  | 
| Characterization of HIV-1 DNA in blood monocytes |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, HAART, Viral DNA test positive-10063306, Blood HIV RNA 10049826, Treatment Experienced