HIV Infections
Conditions
Keywords
HIV-1, Tat, latency, latency reversing agents, transcription
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.
Detailed description
20 ml of blood (5 tubes of 4 ml each) will be collected from 24 people living with HIV who are on ART. The inclusion criteria for this study are: being HIV-positive, having an undetectable viral load for more than 12 months, and having a history of very low T-CD4 counts (nadir \< 200 cells/mm³). In the lab, investigators will isolate immune cells (PBMCs) from the blood using a special technique. These cells will then be placed in small wells and treated with LRAs for 18-20 hours. Investigators will measure the virus produced in the cell supernatant using two methods: q-RT-PCR for viral RNA and p24 ELISA for viral protein. The results will be analyzed using conventional statistical methods.
Interventions
BIOLOGICALBlood Sampling
20 ml of blood (5 tubes of 4 ml) will be collected once.
Sponsors
Centre National de la Recherche Scientifique, France
Université Montpellier
University Hospital, Montpellier
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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 * Participating in another research project with an ongoing exclusion period * Refusal to participate in research * Subject not affiliated to a social security scheme, or not benefiting from such a scheme.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantity of p24 in the cell supernatant 18-20 hours after the addition of the LRAs (Latency Reversing Agents) | INCLUSION VISIT | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantity of viral RNA in the cell supernatant 18-20 hours after the addition of LRAs. | INCLUSION VISIT | quantity of viral RNA in the cell supernatant 18-20 hours after the addition of LRAs. |
| Measure the effective dose of D10 to reverse the latency of latent HIV-infected PBMCs | INCLUSION VISIT | effective dose of D10 to reverse the latency of latent HIV-infected PBMCs |
Countries
France
Contacts
Primary ContactAlain MAKINSON, Pr
Backup ContactBruno BEAUMELLE
Outcome results
None listed