Study of Recovery of Intestinal CD4+ and Th17 T Cells in HIV-infected Individuals on Short-term Antiretroviral Therapy

HIV Infection and Gut Mucosal Immune Function: Longitudinal Analyses of Intestinal CD4+ and Th17 T Cells in HIV-infected Individuals on Short-term Antiretroviral Therapy

HIV infection is associated with a state of chronic, generalized immune activation that has been shown in many studies to be a key predictor of progression to AIDS. The molecular, cellular, and pathophysiological mechanisms underlying the HIV-associated immune activation are complex and still poorly studied. There is, however, growing consensus that both viral and host factors contribute to this phenotype, with emphasis on the role played by the mucosal immune dysfunction (and consequent microbial translocation). Moreover if it is known that in HIV-infected individuals, a severe depletion of intestinal cluster of differentiation 4 (CD4+) T-cells, is associated with loss of epithelium integrity, microbial translocation and systemic immune activation, the kinetics of intestinal CD4+ T-cell reconstitution under combined antiretroviral therapy (cART) remains poorly understood.

This study sought to evaluate the reconstitution of intestinal CD4+ T-cells, including Th1 and Th17, in blood and colon samples collected from HIV-infected individuals before and after a short term cART.

Study Overview

• Status: Unknown
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Tenofovir-Emtricitabine plus Lopinavir/Ritonavir or Darunavir/Ritonavir

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • RM
    • Rome, RM, Italy, 00161
      • Department of Public Health and Infectious Diseases, University of Rome "Sapienza", Italy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• naïve for antiretroviral treatment
• met the criteria to start cART according to International Guidelines
• written informed consent signed

Exclusion Criteria:

• treatment with glucocorticosteroids and any immune modulating medication for more than seven days in the previous month
• any past or current systemic malignancy, history of inflammatory diseases of the small or large intestine
• pregnancy
• anemia, use of anticoagulants, and any contraindications to phlebotomy or colonoscopy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: naïve for cART that met the criteria to start treatment; patients naïve for antiretroviral treatment that met the criteria to start cART according to International Guidelines. These patients will be studied for primary and secondary outcomes after a short term antiretroviral therapy.

Drug: Tenofovir-Emtricitabine plus Lopinavir/Ritonavir or Darunavir/Ritonavir; Conventional antiretroviral therapy started in naïve patients for antiretroviral treatment that met the criteria to start cART according to International Guidelines. The antiretroviral treatment consisted in a tenofovir-emtricitabine NRTI backbone (TDF/FTC, 300/200 mg/ml, once a day) plus boosted protease inhibitor, lopinavir/ritonavir (LPV/r, 400/100 mg twice a day) or darunavir/ritonavir (DRV/r 800/100mg once a day).; Other Names: Truvada; Prezista; Norvir; Kaletra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of number of total Th1 and Th17 CD4+ T-cells (cell/mmc and %) in colon samples between T0 (before start of cARV) and T1 (after 6 months of cARV)	recovery of total Th1 and Th17 CD4+ T-cells (cell/mmc and %) in gut mucosa after 6 months of cARV)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of number of total Th1 and Th17 CD4+ T-cells (cell/mmc and %) in blood samples between T0 (before start of cARV) and T1 (after 6 months of cARV)	recovery of total Th1 and Th17 CD4+ T-cells (cell/mmc and %) in peripheral blood after 6 months of cARV)	6 months

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Collaborators: Istituto Superiore di Sanità
• Investigators: Principal Investigator: Vincenzo Vullo, MD, University of Roma La Sapienza

Publications and helpful links

General Publications

• d'Ettorre G, Baroncelli S, Micci L, Ceccarelli G, Andreotti M, Sharma P, Fanello G, Fiocca F, Cavallari EN, Giustini N, Mallano A, Galluzzo CM, Vella S, Mastroianni CM, Silvestri G, Paiardini M, Vullo V. Reconstitution of intestinal CD4 and Th17 T cells in antiretroviral therapy suppressed HIV-infected subjects: implication for residual immune activation from the results of a clinical trial. PLoS One. 2014 Oct 23;9(10):e109791. doi: 10.1371/journal.pone.0109791. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): March 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: March 17, 2014
• First Submitted That Met QC Criteria: March 26, 2014
• First Posted (Estimate): March 27, 2014

Study Record Updates

• Last Update Posted (Estimate): March 27, 2014
• Last Update Submitted That Met QC Criteria: March 26, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: HIV infection; chronic inflammation; HAART; antiretroviral therapy; Th1; Th17; cART; microbial translocation; CD4+; GUT
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lopinavir; Darunavir
• Other Study ID Numbers: DPHID-UniRoma01