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

• ClinicalTrials.gov Identifier: NCT02526940
• Recruitment Status: Completed
• First Posted: August 18, 2015
• Last Update Posted: November 1, 2015
• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Saint Etienne

Tracking Information

• First Submitted Date: August 17, 2015
• First Posted Date: August 18, 2015
• Last Update Posted Date: November 1, 2015
• Study Start Date: May 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2015)

HIV DNA load in rectal biopsies [ Time Frame: day 1 ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 17, 2015)

• HIV DNA load in blood peripheral blood mononuclear cell (PBMC) [ Time Frame: Day 1 ]
  Comparison of HIV DNA load (copies/106 cells) in blood PBMC between 3 groups of patients (10 per group) according to their blood CD4 cells count at the time of initiation of HAART : <200, 200-300 and >350/mm3
• HIV RNA load in blood PBMC [ Time Frame: Day 1 ]
  Comparison of HIV RNA load (copies/106 cells) in blood PBMC between 3 groups of patients (10 per group) according to their blood CD4 cells count at the time of initiation of HAART : <200, 200-300 and >350/mm3
• HIV RNA load in rectal biopsies [ Time Frame: Day 1 ]
  Comparison of HIV RNA 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 HAART : <200, 200-300 and >350/mm3
• Cellular composition in rectal biopsies [ Time Frame: Day 1 ]
  Comparison of Cellular composition in rectal biopsies between 3 groups of patients (10 per group) according to their blood CD4 cells count at the time of initiation of HAART : <200, 200-300 and >350/mm3. Cellular composition is a outcome measure : expression of CD3, CD4, CD8, CD27, CD45, CCR5 by flow cytometry
• Cellular composition in blood PBMC [ Time Frame: Day 1 ]
  Comparison of Cellular composition in blood PBMCbetween 3 groups of patients (10 per group) according to their blood CD4 cells count at the time of initiation of HAART : <200, 200-300 and >350/mm3. Cellular composition is a outcome measure : expression of CD3, CD4, CD8, CD27, CD45, CCR5 by flow cytometry

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Impact of Pre-ART Blood CD4+ T Cell Level on the Rectal Reservoir in Long-term HIV-1 Treated Men
• Official Title: Impact of Pre- Antiretroviral Therapy (ART) Blood Cluster of Differentiation (CD)4+ T Cell Level on the Rectal Reservoir in Long-term HIV-1 Treated Men
• 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.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

blood specimen and rectal biopsies

• 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.
• Condition: Human Immunodeficiency Virus

Intervention

• Procedure: rectal biopsies
  6 rectal biopsies
• Other: Blood samples
  Blood samples

Study Groups/Cohorts

• 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

  Interventions:

  • 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
  Interventions:

  • 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

  Interventions:

  • Procedure: rectal biopsies
  • Other: Blood samples

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2015): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02526940
• Other Study ID Numbers: 1308020
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
• Study Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Not Provided

Investigators

• Principal Investigator: Frederic LUCHT, PhD; CHU SAINT-ETIENNE

• PRS Account: Centre Hospitalier Universitaire de Saint Etienne
• Verification Date: October 2015