Development of a New Family of HIV Latency Regulators (LRAs) Targeting the Tat Viral Protein

NCT06441123 | Recruiting

• 1 other identifier: RECHMPL23_0276
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Antiretroviral therapy (ART) prevents HIV from multiplying. However, if people living with HIV stop taking ART, the virus quickly reappears in their blood due to the random activation of hidden infected cells. These hidden cells contain HIV that is not active and do not produce the virus. These cells are a major challenge in finding a cure for HIV. One of the most promising ways to get rid of these hidden infected cells is by activating them with special drugs called latency-reversing agents (LRAs). This process, known as the "shock-and-kill" strategy, involves waking up the hidden virus ("shock" phase) so that it can be destroyed by the body's immune system or by the virus itself ("kill" phase). Investigators are developing new LRAs that target and activate a viral protein called Tat, which is necessary for the virus to start producing again and for reversing its dormant state.The lead compound, named D10, is the first of its kind to target the Tat protein. This compound has been patented and has shown activity in activating the virus in lab-grown cells. Now, investigators need to test its effectiveness on real target cells from people living with HIV.

Conditions

HIV Infections

Keywords

HIV-1; Tat; latency; latency reversing agents; transcription

Outcome Measures

Primary Outcomes (1)

• Quantity of p24 in the cell supernatant 18-20 hours after the addition of the LRAs (Latency Reversing Agents)

  Viral production is considered significant if the signal obtained from the p24 ELISA of these supernatants is more than twice the background observed in the absence of LRA

  INCLUSION VISIT

Secondary Outcomes (2)

• Quantity of viral RNA in the cell supernatant 18-20 hours after the addition of LRAs.

  INCLUSION VISIT

• Measure the effective dose of D10 to reverse the latency of latent HIV-infected PBMCs

  INCLUSION VISIT

Interventions

Blood Sampling BIOLOGICAL

20 ml of blood (5 tubes of 4 ml) will be collected once.

Eligibility Criteria

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

Study Population

The target population is aviremic HIV-positive individuals, with no age criterion, having a long history of HIV infection (nadir \< 200 CD4/µL

You may qualify if:

• Patient aged 18 years or older
• HIV-positive
• On ART (antiretroviral therapy)
• HIV-1 RNA undetectable for more than 12 months
• Nadir CD4 count \< 200/µL

You may not qualify if:

• Lack of antiretroviral treatment
• Immunosuppressive treatments
• History of cancer less than 5 years old
• Pregnant or breast-feeding women
• Persons protected by law (under guardianship or curators), persons under court protection
• Refusal to participate in research
• Subject not affiliated to a social security scheme, or not benefiting from such a scheme.

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• Centre National de la Recherche Scientifique, France: collaborator
• Université Montpellier: collaborator

Study Sites (1)

CHU de MONTPELLIER

Montpellier, 34090, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

20 ml of blood (5 tubes of 4 ml each) from 24 people living with HIV who are on AntiRetroviral Therapy

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

Central Study Contacts

Alain MAKINSON, Pr

CONTACT

04 67 33 83 40; a-makinson@chu-montpellier.fr

Bruno BEAUMELLE

CONTACT

bruno.beaumelle@irim.cnrs.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: June 4, 2024
• Study Start: February 10, 2025
• Primary Completion (Estimated): February 10, 2027
• Study Completion (Estimated): February 10, 2027
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)