Impact of Pre-ART Blood CD4+ T Cell Level on the Rectal Reservoir in Long-term HIV-1 Treated Men

NCT02526940 | Completed

• 1 other identifier: 1308020
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Although combined antiretroviral therapy (cART) has dramatically improved quality of life and lifespan of HIV infected individuals, it still fails to eliminate viral reservoirs. The Gut Associated Lymphoid Tissue (GALT) is the largest reservoir of HIV-1, as it harbors most of HIV target cells as activated memory Cluster of differentiation (CD)4+/CCR5+ T cells. Intestinal T and B cells express α4β7 integrin, a gut mucosal homing receptor which binds to gp120 HIV-1 envelope facilitating the infection of intestinal T cells and the early establishment of the gut HIV reservoir. Intensive viral replication in the GALT leads to an early impairment of mucosal immunity, due to the severe CD4+ T cells depletion, that could be also explained by a lack of recruitment in the gut. Among T cells, interleukin-(IL-)17 secreting CD4+ T cells (Th17) are particularly depleted during HIV infection. This depletion could be associated with HIV progression since these cells play a crucial role in the maintenance of mucosal immunity. A dysbalance of the Th17/Treg ratio may reflect the loss of the intestinal epithelial barrier integrity. These damages are responsible for an increase in microbial translocation, which is associated with immune activation and progression to AIDS. Several recent studies have shown that cART initiation during acute or early HIV-1 infection reduces HIV DNA reservoir size and improves immune reconstitution in blood. Post-treatment controllers, who started long-term cART early after HIV infection, have very low levels of HIV DNA in peripheral blood mononuclear cells, similarly to elite controllers. Unlike most HIV-infected individuals, they maintain an undetectable plasmatic viral load after several years of cART interruption, suggesting that a weak reservoir is a prerequisite to achieve a functional cure. By extrapolation, it could be hypothesized that the gut viral reservoir is also decreased and that mucosal immunity is restored when cART is initiated during primary phase of infection. The gut viral reservoir begins to form within the first days after HIV exposure, and grows during acute HIV infection. Similarly, intestinal T cells are depleted very early after infection, due to high viral replication, host immune response and bystander effects. Most studies also concluded that long-term and optimal treatment can't fully restore mucosal immunity. These observations led us to study the impact of time of cART start on the size of viral reservoir and on immune reconstitution in the gut. For this, we analyzed the virological and immunological characteristics of the rectal HIV reservoir of long-term treated patients regarding their blood CD4+ T cells count at the time of cART initiation.

Conditions

Human Immunodeficiency Virus

Keywords

Human Immunodeficiency Virus; HIV; HAART; Highly Active antiretroviral therapy; GALT; Gut Associated Lymphoid Tissue; reservoir; rectum

Outcome Measures

Primary Outcomes (1)

• HIV DNA load in rectal biopsies

  Comparison of HIV DNA load (copies/106 cells) in rectal biopsies between 3 groups of patients (10 per group) according to their blood CD4 cells count at the time of initiation of Highly Active Antiretroviral Therapy (HAART) : \<200, 200-300 and \>350/mm3

  day 1

Secondary Outcomes (5)

• HIV DNA load in blood peripheral blood mononuclear cell (PBMC)

  Day 1

• HIV RNA load in blood PBMC

  Day 1

• HIV RNA load in rectal biopsies

  Day 1

• Cellular composition in rectal biopsies

  Day 1

• Cellular composition in blood PBMC

  Day 1

Study Arms (3)

blood CD4 cells count < 200/mm3

patients with blood CD4 cells count at the time of initiation of HAART\< 200/mm3. Six rectal biopsies and blood samples collected for each patient treated by HAART more than 1 year and less than 4 years

Procedure: rectal biopsies; Other: Blood samples

blood CD4 cells count : 200 - 300/mm3

patients with blood CD4 cells count at the time of initiation of HAART between 200 and 300/mm3 Six rectal biopsies and blood samples collected for each patient treated by HAART more than 1 year and less than 4 years

Procedure: rectal biopsies; Other: Blood samples

blood CD4 cells count >350/mm3

patients with blood CD4 cells count at the time of initiation of HAART\> 350/mm3. Six rectal biopsies and blood samples collected for each patient treated by HAART more than 1 year and less than 4 years

Procedure: rectal biopsies; Other: Blood samples

Interventions

rectal biopsies PROCEDURE

6 rectal biopsies

blood CD4 cells count : 200 - 300/mm3; blood CD4 cells count < 200/mm3; blood CD4 cells count >350/mm3

Blood samples OTHER

Blood samples

blood CD4 cells count : 200 - 300/mm3; blood CD4 cells count < 200/mm3; blood CD4 cells count >350/mm3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

3 groups of men elaborated on the basis of their blood CD4+ T cells count at the time of cART initiation: \>350; 350-200; \<200, respectively.

You may qualify if:

• Seropositive for HIV
• Under HAART since at least one and less than 4 years
• No blood HIV RNA rebound during the therapy
• Indication of Human Papilloma Virus (HPV) screening by anal rectoscopy
• Signature of the informed consent form

You may not qualify if:

• Patient under tutelage
• No signature of the informed consent form
• No CD4 cell count available at the time of HAART initiation
• One or several viral rebound(s) during therapy
• Coinfection by hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Hemostasis disorders, anticoagulant therapy
• No medical indication of rectoscopy
• Inflammatory bowel disease
• No understanding of the protocol

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead

Study Sites (1)

CHU Saint-ETIENNE

Saint-Etienne, 42055, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood specimen and rectal biopsies

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Frederic LUCHT, PhD

  CHU SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2015
• First Posted: August 18, 2015
• Study Start: May 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: November 2, 2015

Record last verified: 2015-10

Locations

FR (1)