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

Hiv Infection Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01952587
• Other study ID #: ANRS EP 53 X LIBRIS
• Secondary ID: 2013-A00954-41
• Status: Completed
• Phase: N/A
• First received: August 5, 2013
• Last updated: June 30, 2015
• Start date: November 2013
• Est. completion date: June 2015

Study information

• Verified date: June 2015
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: ANSM - Agence nationale de sécurité du médicament et des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hiv Infection

Intervention

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

Locations

Country	Name	City	State
France	Purpan Hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	day 1	No
Secondary	Frequency (%) of cells expressing the "A" and "T" alleles of TRL7 in interferon-alpha producing cells		day 1 and month 3	No

External Links

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