X-linked Biological Response to HIV Sensing: the ANRS EP 53 Study (X LIBRIS)
Primary Purpose
Hiv Infection
Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
A peripheral blood sample
Sponsored by
About this trial
This is an interventional basic science trial for Hiv Infection
Eligibility Criteria
Inclusion Criteria:
- Caucasian Female
- HIV-1 infection (ELISA and western-blot tests)
- HIV-infection through the sexual route before 50 years-old
- Continuous antiretroviral therapy for more than 6 months
- Plasma HIV-1 RNA <50 copies/ml in the last 6 months
- Age >18-year old
- Health insurance
- Informed consent
Exclusion Criteria:
- HIV-infection through vertical or parenteral routes
- Chronic infectious disease, notably HCV infection (hepatitis C virus)
- Acute infectious disease
- Auto-immune disease
- Absence of social security (health insurance)
- Pregnant or breastfeeding woman
- Incapable adult
Sites / Locations
- Purpan Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
HIV-infected women
Healthy control women
Arm Description
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.
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
Outcomes
Primary Outcome Measures
Frequency (%) of subjects carrying the TRL7 c.32A>T SNP in HIV-infected and healthy women
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
Full Information
NCT ID
NCT01952587
First Posted
August 5, 2013
Last Updated
June 30, 2015
Sponsor
ANRS, Emerging Infectious Diseases
1. Study Identification
Unique Protocol Identification Number
NCT01952587
Brief Title
X-linked Biological Response to HIV Sensing: the ANRS EP 53 Study
Acronym
X LIBRIS
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
November 2013 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hiv Infection
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HIV-infected women
Arm Type
Other
Arm Description
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.
Arm Title
Healthy control women
Arm Type
Other
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
A peripheral blood sample
Intervention Description
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
Primary Outcome Measure Information:
Title
Frequency (%) of subjects carrying the TRL7 c.32A>T SNP in HIV-infected and healthy women
Description
arguing in favor of role of impaired production of IFN alpha by pDCs in the risk of becoming infected by HIV 1
Time Frame
day 1
Secondary Outcome Measure Information:
Title
Frequency (%) of cells expressing the "A" and "T" alleles of TRL7 in interferon-alpha producing cells
Time Frame
day 1 and month 3
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Caucasian Female
HIV-1 infection (ELISA and western-blot tests)
HIV-infection through the sexual route before 50 years-old
Continuous antiretroviral therapy for more than 6 months
Plasma HIV-1 RNA <50 copies/ml in the last 6 months
Age >18-year old
Health insurance
Informed consent
Exclusion Criteria:
HIV-infection through vertical or parenteral routes
Chronic infectious disease, notably HCV infection (hepatitis C virus)
Acute infectious disease
Auto-immune disease
Absence of social security (health insurance)
Pregnant or breastfeeding woman
Incapable adult
Facility Information:
Facility Name
Purpan Hospital
City
Toulouse
Country
France
12. IPD Sharing Statement
Links:
URL
http://anrs.fr
Description
Related Info
Learn more about this trial
X-linked Biological Response to HIV Sensing: the ANRS EP 53 Study
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