HIV Sequencing After Treatment Interruption to Identify the Clinically Relevant Anatomical Reservoir (HIV-STAR)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02641756|
Recruitment Status : Completed
First Posted : December 29, 2015
Last Update Posted : January 28, 2020
The main goal of this study is to identify and characterise the anatomical component of the replication competent HIV-1 (Human Immunodeficiency Virus-1) reservoir.
The investigators hypothesize that the clinically relevant HIV-1 reservoir is hiding in various but specific anatomic compartments and is able to rebound when therapy is stopped.
This reservoir is probably smaller than the HIV-1 reservoir hiding in the blood but could be more transcriptional active because of its specific environment, possibly influenced by lower concentrations of the antiretroviral therapy.
The current proposal will, for the first time, identify the source of the viral reservoir by phylogenetically backtracking the viral genome of the rebounding virus to the sequences of viral DNA (DeoxyriboNucleic Acid) in different anatomical compartments. The subsequent characterization of the viral reservoir markers (size, integration sites, methylation profile, stimulation and inhibition assays) will enable us to understand how this viral rebound occurred.
|Condition or disease||Intervention/treatment||Phase|
|HIV||Other: treatment interruption after in depth sampling under CART||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||In Depth Sampling and Subsequent Treatment Interruption to Identify the Anatomical Reservoir|
|Actual Study Start Date :||April 2016|
|Actual Primary Completion Date :||July 2018|
|Actual Study Completion Date :||August 2019|
Experimental: Study Population
This is a single arm study. The investigators will include 10 HIV positive patients under chronic CART (combined antiretroviral therapy).
The intervention will consist on treatment interruption after in depth sampling under CART
Other: treatment interruption after in depth sampling under CART
The participants will undergo in depth sampling under CART to characterise the HIV reservoir in different anatomical compartments. Subsequently an experimental viral rebound, by a brief therapy stop, will help us identify the clinically relevant viral reservoir by doing phylogenetic analysis on the rebounding virus and on the virus found in the different compartments under CART.
- Phylogenetic analysis of the virus found in the different compartments under treatment and of the virus in the plasma at viral rebound. [ Time Frame: 24 months ]Genetically link the viral reservoir in different anatomical reservoirs to the rebounding virus found in the plasma after therapy-stop by doing phylogenetic analysis. This will be done by a method called single proviral sequencing.
- Number of patients with and the severity of adverse events that are related to the study intervention, graded according to NCI CTCAE Version 4.0 [ Time Frame: 24 months ]Assess safety of the experimental treatment interruption for future clinical trials. Confirmation of the safety of a treatment interruption strategy in selected patients will be based on the number and intensity of AEs (adverse events) graded according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE) on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death). The investigators will also evaluate psychological effects of the treatment interruption by a questionnaire.
- Evaluation of the reservoir replenishment by quantifying the viral reservoir under CART (combined antiretroviral therapy) in various anatomic compartments.(Total HIV DNA, integrated HIV DNA, Cell-associated-HIV RNA, viral outgrowth assay). [ Time Frame: 24 months ]Assessment of the viral reservoir magnitude prior and after treatment interruption by quantification of viral reservoir by ultrasensitive PCR (polymerase chain reaction) methods and replication competence of the virus by reactivation assays.
- Therapeutic drug monitoring assessed by drug concentrations measured in the different compartments [ Time Frame: 24 months ]assess drug concentrations in different compartments and its significance in maintaining the HIV reservoir
- Assessment of the kinetics of HIV viral load rebound after treatment interruption based on the repetitive plasma viral load measurements. [ Time Frame: 6 months ]The kinetics will be on the plasma viral load (expressed in copies/ml) measured two-weekly until viral rebound.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02641756
|Gent, Oost-Vlaanderen, Belgium, 9000|
|Principal Investigator:||Linos Vandekerckhove, Prof||UZ Gent - U Gent|