HUSH Restriction in HIV Infected Patients

NCT04172480 | Unknown

• 1 other identifier: ANRS RF 004
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

HIV eradication faces a major obstacle that is viral persistence in latent reservoir cells despite antiretroviral therapy. Epigenetic repression plays a central role in viral transgene latency and several epigenetic regulators have been involved in this process. Among them, the "Human Silencing Hub" or HUSH complex, composed of Tasor, MPP8 and periphilin, has been shown to recruit the H3K9me3 methyltransferase "SET domain bifurcated 1" (SETDB1) and is therefore responsible for genes' epigenetic repression. Our recent results highlight the ability of Vpx from HIV-2/SIVsmm to counteract HUSH and to reactivate latent viruses in a latency model. We propose here to study HUSH activity along pathogenesis.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (3)

• Viremia

  Intracellular HIV RNA load expressed in number of copies / ml

  Baseline

• Total HIV DNA and integrated HIV DNA

  Quantification by qPCR

  Baseline

• Hush activity

  Transcription rate of cellular genes targeted by HUSH by qRT-PCR

  Baseline

Study Arms (3)

acute HIV1 infection

Patient infected by HIV1, prior treatment initiation

Other: Blood sampling

chronic HIV1 infection

Patient infected by HIV1, untreated or without treatment since at least 3 months

Other: Blood sampling

HIV2 infection

Patient infected by HIV2, untreated or without treatment since at least 3 months

Other: Blood sampling

Interventions

Blood sampling OTHER

Peripheral blood sampling on EDTA

HIV2 infection; acute HIV1 infection; chronic HIV1 infection

Eligibility Criteria

• Age: 15 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Population infected either by HIV1 or HIV2

You may qualify if:

• Symptomatic or asymptomatic acute HIV1 infection
• Age above 15 years old
• Chronic HIV1 infection
• Age above 18 years old
• No ARV treatment since at least 3 month (regardless the reason)
• HIV2 Infection
• Age above 18 years old
• No ARV treatment since at least 3 month (regardless the reason)

You may not qualify if:

• HIV1 and HIV2 co-infection
• Evolutive intercurrent pathology, in particular active co-infection (i.e. HBV, HCV, tuberculosis, HTLV1)
• Life-threatening pathology

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (3)

Hôpital Bicêtre

Le Kremlin-Bicêtre, 94270, France

NOT YET RECRUITING

Hôtel-Dieu

Paris, 75004, France

RECRUITING

Hôpital Necker

Paris, 75015, France

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

PBMC conserved in RLT Buffer for viral DNA and RNA extraction

MeSH Terms

Conditions

HIV Infections

Interventions

Blood Specimen Collection

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)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: November 21, 2019
• Study Start: October 1, 2019
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2023
• Last Updated: December 20, 2021

Record last verified: 2021-12

Locations

FR (3)