HUSH Restriction in HIV Infected Patients

• Sponsor: ANRS, Emerging Infectious Diseases (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04172480
• Collaborator: (none)
• Enrollment: 50
• Locations: 3
• Anticipated Duration (Months): 48
• Patients Per Site: 16.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Other: Blood sampling

Study Design

• Study Type: Observational
• Anticipated Enrollment: 50 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: HUSH Restriction in HIV Infected Patients
• Actual Study Start Date: Oct 1, 2019
• Anticipated Primary Completion Date: Sep 30, 2023
• Anticipated Study Completion Date: Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
acute HIV1 infection Patient infected by HIV1, prior treatment initiation	Other: Blood sampling; Peripheral blood sampling on EDTA
chronic HIV1 infection Patient infected by HIV1, untreated or without treatment since at least 3 months	Other: Blood sampling; Peripheral blood sampling on EDTA
HIV2 infection Patient infected by HIV2, untreated or without treatment since at least 3 months	Other: Blood sampling; Peripheral blood sampling on EDTA

Outcome Measures

Primary Outcome Measures

1. Viremia [Baseline]

   Intracellular HIV RNA load expressed in number of copies / ml

2. Total HIV DNA and integrated HIV DNA [Baseline]

   Quantification by qPCR

3. Hush activity [Baseline]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for group 1:

• Symptomatic or asymptomatic acute HIV1 infection

• Age above 15 years old

• No ARV treatment prior inclusion (excepted as prophylaxis pre or post exposure)

Inclusion Criteria for group 2:

• Chronic HIV1 infection

• Age above 18 years old

• No ARV treatment since at least 3 month (regardless the reason)

Inclusion Criteria for group 3:

• HIV2 Infection

• Age above 18 years old

• No ARV treatment since at least 3 month (regardless the reason)

Exclusion Criteria for all groups:

• HIV1 and HIV2 co-infection

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

• Life-threatening pathology

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Bicêtre	Le Kremlin-Bicêtre		France	94270
2	Hôtel-Dieu	Paris		France	75004
3	Hôpital Necker	Paris		France	75015

Sponsors and Collaborators

• ANRS, Emerging Infectious Diseases

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ANRS, Emerging Infectious Diseases
• ClinicalTrials.gov Identifier: NCT04172480
• Other Study ID Numbers: ANRS RF 004
• First Posted: Nov 21, 2019
• Last Update Posted: Dec 20, 2021
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: HIV Infections

Study Results

No Results Posted as of Dec 20, 2021