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

NCT02097381 | Unknown DMC

• 1 other identifier: DPHID-UniRoma01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infection

Keywords

HIV infection; GUT; microbial translocation; chronic inflammation; antiretroviral therapy; cART; HAART; Th17; Th1; CD4+

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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)

  6 months

Study Arms (1)

naïve for cART that met the criteria to start treatment

OTHER

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

Interventions

Tenofovir-Emtricitabine plus Lopinavir/Ritonavir or Darunavir/Ritonavir DRUG

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).

Also known as: Truvada, Prezista, Kaletra, Norvir

naïve for cART that met the criteria to start treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Roma La Sapienza: lead
• Istituto Superiore di Sanità: collaborator

Study Sites (1)

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

Rome, RM, 00161, Italy

Location

Related Publications (1)

• 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.

  PMID: 25340778 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Lopinavir; Ritonavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Darunavir; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Tenofovir; Organophosphonates; Organophosphorus Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Furans

Study Officials

• Vincenzo Vullo, MD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, MSc

Study Record Dates

• First Submitted: March 17, 2014
• First Posted: March 27, 2014
• Study Start: April 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 27, 2014

Record last verified: 2014-03

Locations

IT (1)