Trial record 15 of 32 for:    " July 10, 2013":" August 09, 2013"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

X-linked Biological Response to HIV Sensing: the ANRS EP 53 Study (X LIBRIS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT01952587
First received: August 5, 2013
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

Short title :

X-linked biological response to HIV sensing: the ANRS EP 53 study.

Main outcome :

To demonstrate that HIV-infected women carry the TLR7 c.32A>T SNP at a higher frequency than uninfected women, arguing in favor of a role of impaired production of IFN-alpha by pDCs in the risk of becoming infected by HIV-1.

Secondary outcome :

To directly demonstrate at a single cell level that the TLR7 c.32A>T SNP is responsible for a reduce production of IFN-alpha by pDCs after activation of TLR7 by HIV-1 RNA.

Short abstract (public dissemination) :

Male and female display some differences in how their immune system responds to pathogens. This could be related to hormonal or genetic factors located on the X chromosome. This project aims at characterizing X-linked factors that can influence the innate immune response to HIV-1.


Condition Intervention
Hiv Infection
Biological: A peripheral blood sample

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Frequency and Functional Impact of the c.32A>T Genetic Polymorphism of TLR7 in Women Infected With HIV-1 : the ANRS EP53 Study

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Frequency (%) of subjects carrying the TRL7 c.32A>T SNP in HIV-infected and healthy women [ Time Frame: day 1 ] [ Designated as safety issue: No ]
    arguing in favor of role of impaired production of IFN alpha by pDCs in the risk of becoming infected by HIV 1


Secondary Outcome Measures:
  • Frequency (%) of cells expressing the "A" and "T" alleles of TRL7 in interferon-alpha producing cells [ Time Frame: day 1 and month 3 ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: November 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
HIV-infected women
A peripheral blood sample will be collected from HIV-infected women to measure TLR-7 SNP frequency by PCR. IFN-alpha production from pDCs after HIV-1 RNA sensing by TLR7 will also be assessed.
Biological: A peripheral blood sample
A peripheral blood sample will be collected from HIV-infected subjects and healthy control to measure TLR-7 SNP frequency by PCR. IFN-alpha production from pDCs after HIV-1 RNA sensing by TLR7 will also be assessed
Healthy control women
A peripheral blood sample will be collected from healthy women to measure TLR-7 SNP frequency by PCR. IFN-alpha production from pDCs after HIV-1 RNA sensing by TLR7 will also be assessed
Biological: A peripheral blood sample
A peripheral blood sample will be collected from HIV-infected subjects and healthy control to measure TLR-7 SNP frequency by PCR. IFN-alpha production from pDCs after HIV-1 RNA sensing by TLR7 will also be assessed

Detailed Description:

Plasmacytoid dendritic cells (pDCs) are key actors of innate immunity that produce high levels of interferon (IFN)-alpha after activation of their Toll-Like Receptors (TLR) by pathogens. A difference between men and women has recently been shown in the level of IFN-alpha produced by pDCs after TLR activation. The production of IFN-alpha in response to TLR7 activation is higher in the presence of estrogens. This could be responsible for gender differences in the level of plasma HIV-1 RNA, that is lower in female as compared to male by about 50%, and for the sex-based differences in the susceptibility to HIV infection. Besides the role of estrogens, X-linked genetic factors could also be involved in the sex-dependent differences in the TLR7-mediated responses of pDCs. TLR7 gene is located on the X chromosome. A single nucleotide polymorphism (SNP) of the TLR7 gene, c.32A>T, have been associated with accelerated disease progression in male HIV patients, and was found over represented in female HIV as well as HCV patients, suggesting that the T allele is associated with a gender-dependent increase of susceptibility to RNA virus infections. A peripheral blood sample will be collected from HIV-infected women and healthy control to measure TLR-7 SNP frequency by PCR. IFN-alpha production from pDCs after HIV-1 RNA sensing by TLR7 will also be assessed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Caucasian Female
  2. HIV-1 infection (ELISA and western-blot tests)
  3. HIV-infection through the sexual route before 50 years-old
  4. Continuous antiretroviral therapy for more than 6 months
  5. Plasma HIV-1 RNA <50 copies/ml in the last 6 months
  6. Age >18-year old
  7. Health insurance
  8. Informed consent

Exclusion Criteria:

  1. HIV-infection through vertical or parenteral routes
  2. Chronic infectious disease, notably HCV infection (hepatitis C virus)
  3. Acute infectious disease
  4. Auto-immune disease
  5. Absence of social security (health insurance)
  6. Pregnant or breastfeeding woman
  7. Incapable adult
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01952587

Contacts
Contact: Pierre Delobel +335 61 77 75 08
Contact: Jean Charles Guéry +335 62 74 45 45

Locations
France
Purpan Hospital Recruiting
Toulouse, France
Contact: Pierre Delobel         
Principal Investigator: Pierre Delobel         
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
  More Information

Additional Information:
No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT01952587     History of Changes
Other Study ID Numbers: ANRS EP 53 X LIBRIS, 2013-A00954-41
Study First Received: August 5, 2013
Last Updated: July 22, 2014
Health Authority: France: ANSM - Agence nationale de sécurité du médicament et des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on August 27, 2014