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

Not Applicable

Completed

• Conditions: HIV Infection
• Interventions: Procedure: GI endoscopy and GALT biopsies; Biological: A sample of venous blood will also be collected

• Registration Number: NCT01038401
• Lead Sponsor: French National Agency for Research on AIDS and Viral Hepatitis

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-09
• Study First Submitted: 2009-12-22
• Study First Submitted QC: 2009-12-23
• Study First Posted: 2009-12-24
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Status Verified: 2010-07
• Last Update Submitted: 2010-07-13
• Last Update Posted: 2010-07-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HIV-1-infected patients on effective HAART	GI endoscopy and GALT biopsies	-
HIV-1-infected patients on effective HAART	A sample of venous blood will also be collected	-
Non Infected HIV Volunteers	GI endoscopy and GALT biopsies	-
Non Infected HIV Volunteers	A sample of venous blood will also be collected	-

Primary Outcome Measures

Name	Time	Method
Correlation between HIV-1 viral load and CD4+ T lymphopenia in the GALT.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

ANRS center from Toulouse; 🇫🇷 Toulouse, France