HUSH Restriction in HIV Infected Patients

• Conditions: HIV Infections

• Registration Number: NCT04172480
• Lead Sponsor: ANRS, Emerging Infectious Diseases

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-10-01
• Study First Submitted: 2019-11-19
• Study First Submitted QC: 2019-11-19
• Study First Posted: 2019-11-21
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-17
• Last Update Posted: 2021-12-20
• Primary Completion: 2023-09-30
• Study Completion: 2023-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Viremia	Baseline	Intracellular HIV RNA load expressed in number of copies / ml
Total HIV DNA and integrated HIV DNA	Baseline	Quantification by qPCR
Hush activity	Baseline	Transcription rate of cellular genes targeted by HUSH by qRT-PCR

Trial Locations

Locations (3)

Hôpital Bicêtre; 🇫🇷 Le Kremlin-Bicêtre, France

Hôtel-Dieu; 🇫🇷 Paris, France

Hôpital Necker; 🇫🇷 Paris, France