Clinical trial NCT01038401: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infection
Keywords: HIV infection
HAART
Viral DNA test positive-10063306
Blood HIV RNA 10049826
Treatment Experienced
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
First posted: 2009-12-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Correlation between HIV-1 viral load and CD4+ T lymphopenia in the GALT.
Secondary outcomes:
measure: HIV-1 DNA load in the GALT vs blood CD4+ T cells
measure: HIV-1 tropism in the GALT vs blood CD4+ T cells
measure: Characterization of residual HIV-1 in the plasma < 40 copies/ml
measure: Characterization of HIV-1 DNA in blood monocytes
Other outcomes:
Locations:
city: Toulouse
country: France
facility: ANRS center from Toulouse
Study officials:
affiliation: CHU Toulouse
name: MASSIP Patrice
role: PRINCIPAL_INVESTIGATOR
References: