HIVHIV-STARNCT02641756
HIV Sequencing After Treatment Interruption to Identify the Clinically Relevant Anatomical Reservoir
A study testing treatment interruption after in depth sampling under CART in people with HIV, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV
- What is being tested?
- treatment interruption after in depth sampling under CART
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteBelgium
- Study dates
- Apr 2016to Aug 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented HIV-1 infection, subtype B
- Able and willing to provide written informed consent
- Age = or >18 years < 65 years
- Nadir CD4 (cluster of differentiation 4) count >=300/µl. Cluster of differentiation 4 (CD4) count at screening > 500/μl
- Patient should take antiretroviral therapy (ART) for at least 2 years with no changes in the ART for at least 90 days prior to study entry. Patients should be on an integrase inhibitor + 2 nucleoside analogs based regimen or PI based regimen.
- Patient should have a viral load < 20 copies/ml determined by CobasTaqMan HIV-1 test v2.0 assay for at least 2 years. (Occasional "blips" will be permitted) (A blip is defined as an intermittent viremic episode with a viral load above detection level but below 200 copies/ml and a return to an undetectable level in a next control, if more than six months prior to the study entry)
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- Last viral load undetectable
- Ability to attend the complete schedule of assessments and patient visits. Ability and willingness to have blood and tissue samples collected and stored indefinitely and used for various research purposes. Women of childbearing potential or their partner should use double barrier contraception during the study. Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or bilateral salpingectomy), will need a negative serum or urine pregnancy test within 48 hours prior to study entry.
- Note: Acceptable documentation of hysterectomy and bilateral oophorectomy, bilateral salpingectomy, tubal micro-inserts, partner who has undergone vasectomy, and menopause is participant-reported history. All participants must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, or in vitro fertilization). Participants must agree to use barrier protection for all sexual activity and if participating in sexual activity that could lead to pregnancy, the participant/partner must use at least two reliable forms of contraceptives (condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an intra-uterine device (IUD); or hormone-based contraception) during the study.
Who cannot join
- Previous or current history of opportunistic infection. (AIDS defining events as defined in category C of the Center for Disease Control and Prevention (CDC) clinical classification).
- History of resistance to antiretroviral drugs, documented by genotyping.
- Hepatitis B surface antigen positive or Hepatitis B virus (HBV) viral load positive in the past and no evidence of subsequent seroconversion (=HBV antigen or viral load negative and positive HBV surface antibody).
- Hepatitis C virus (HCV) antibody positive result within 60 days prior to study entry or, if the HCV antibody result is negative, a positive HCV RNA (Ribonucleic Acid) result within 60 days prior to study entry
- Significant risk of HIV superinfection during treatment interruption.
- Current or known history of cardiomyopathy or significant ischemic or cerebrovascular disease.
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- History of HIV-related thrombocytopenia.
- Active renal disease (defined as a glomerular filtration rate (calculated by Cockcroft Gault equation) below 50ml/min or the presence of HIV-associated nephropathy (HIVAN) in the past medical history.
- Current or known history of cancer (with the exception of in situ cervix carcinoma or squamous cell carcinoma of the skin) within five years prior to screening.
- Pregnancy or breastfeeding.
- Any conditions, including psychiatric and psychological disorders, which will in the opinion of the investigator interfere with the trial conduct or safety of the participant.
- Previous participation in a trial evaluating an immune modulating agent
- Abnormal laboratory tests results at screening:
- Confirmed Hemoglobin <11g/dl for women and <12 g:dl for men
- Confirmed platelet count < 100000/l
- Confirmed neutrophil count <1000/μl
- Confirmed aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2x Upper Limit of Normal (ULN)
- The following treatment will be prohibited three months before screening and during the course of the study:
- immunosuppressive drugs (inclusive corticosteroids) with the exception of drugs used for topical use.
- Immunomodulatory drugs including but not limited to Granulocyte colony stimulating factors, Granulocyte-monocyte stimulating factor, interleukin 2, 7 \& 15.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 60 days prior to entry.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: In Depth Sampling and Subsequent Treatment Interruption to Identify the Anatomical Reservoir
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.
Read more
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.
- Conditions
- HIV
- Being tested
- treatment interruption after in depth sampling under CART
- Keywords
- HIV reservoir, phylogenetic analysis, sequencing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
treatment interruption after in depth sampling under CARTOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Study Population | Experimental | 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 Receives: Other: treatment interruption after in depth sampling under CART |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phylogenetic analysis of the virus found in the different compartments under treatment and of the virus in the plasma at viral rebound.
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.
Measured: 24 months
Secondary outcomes (7)
Number of patients with adverse events that are related to the study intervention, graded according to NCI CTCAE Version 4.0
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).
Measured: 24 months
The severity of adverse events that are related to the study intervention, graded according to NCI CTCAE Version 4.0
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).
Measured: 24 months
Psychological effects of treatment interruption
The investigators will evaluate psychological effects of the treatment interruption by a questionnaire.
Measured: 24 months
Evaluation of the reservoir replenishment by quantifying the viral reservoir under combined antiretroviral therapy (CART) in various anatomic compartments.(Total HIV DNA, integrated HIV DNA, Cell-associated-HIV RNA).
Assessment of the viral reservoir magnitude prior and after treatment interruption by quantification of viral reservoir by ultrasensitive polymerase chain reaction (PCR) methods.
Measured: 24 months
Evaluation of the reservoir replenishment by quantifying the viral reservoir under combined antiretroviral therapy (CART) in various anatomic compartments.(viral outgrowth assay).
Assessment of the viral reservoir magnitude prior and after treatment interruption by replication competence of the virus by reactivation assays.
Measured: 24 months
Therapeutic drug monitoring assessed by drug concentrations measured in the different compartments
assess drug concentrations in different compartments and its significance in maintaining the HIV reservoir
Measured: 24 months
Assessment of the kinetics of HIV viral load rebound after treatment interruption based on the repetitive plasma viral load measurements.
The kinetics will be on the plasma viral load (expressed in copies/ml) measured two-weekly until viral rebound.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study startApr 2016
- Primary completionJul 2018
- Study completionAug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Linos Vandekerckhove, Prof, Principal investigator, UZ Gent - U Gent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02641756
- Sponsor's protocol ID
- IIS 52777
- Acronym
- HIV-STAR
- Status last verified
- Sep 2019
- First submitted
- 9 Dec 2015
- Last updated
- 7 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Cole B, Lambrechts L, Boyer Z, Noppe Y, De Scheerder MA, Eden JS, Vrancken B, Schlub TE, McLaughlin S, Frenkel LM, Palmer S, Vandekerckhove L. Extensive characterization of HIV-1 reservoirs reveals links to plasma viremia before and during analytical treatment interruption. Cell Rep. 2022 Apr 26;39(4):110739. doi: 10.1016/j.celrep.2022.110739.
PubMed 35476994De Scheerder MA, Van Hecke C, Zetterberg H, Fuchs D, De Langhe N, Rutsaert S, Vrancken B, Trypsteen W, Noppe Y, Van Der Gucht B, Pelgrom J, Van Wanzeele F, Palmer S, Lemey P, Gisslen M, Vandekerckhove L. Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption. J Antimicrob Chemother. 2020 May 1;75(5):1311-1320. doi: 10.1093/jac/dkaa003.
PubMed 32053203
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Depth Sampling and Subsequent Treatment Interruption to Identify the Anatomical Reservoir
- ClinicalTrials.gov ID
- NCT02641756
- Acronym / sponsor ID
- HIV-STAR / IIS 52777
- Conditions
- HIV
- Keywords
- HIV reservoir, phylogenetic analysis, sequencing
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Apr 2016 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 29 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Population | Experimental | Other: treatment interruption after in depth sampling under CARTThis 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Documented HIV-1 infection, subtype B
- Able and willing to provide written informed consent
- Age = or >18 years < 65 years
- Nadir CD4 (cluster of differentiation 4) count >=300/µl. Cluster of differentiation 4 (CD4) count at screening > 500/μl
- Patient should take antiretroviral therapy (ART) for at least 2 years with no changes in the ART for at least 90 days prior to study entry. Patients should be on an integrase inhibitor + 2 nucleoside analogs based regimen or PI based regimen.
Key exclusion criteria (22 listed)
- Previous or current history of opportunistic infection. (AIDS defining events as defined in category C of the Center for Disease Control and Prevention (CDC) clinical classification).
- History of resistance to antiretroviral drugs, documented by genotyping.
- Hepatitis B surface antigen positive or Hepatitis B virus (HBV) viral load positive in the past and no evidence of subsequent seroconversion (=HBV antigen or viral load negative and positive HBV surface antibody).
- Hepatitis C virus (HCV) antibody positive result within 60 days prior to study entry or, if the HCV antibody result is negative, a positive HCV RNA (Ribonucleic Acid) result within 60 days prior to study entry
- Significant risk of HIV superinfection during treatment interruption.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| treatment interruption after in depth sampling under CARTThe 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. | Other | Study Population |
Primary outcome
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.
7 secondary outcomes
Number of patients with adverse events that are related to the study intervention, graded according to NCI CTCAE Version 4.0
Time frame: 24 months
The severity of adverse events that are related to the study intervention, graded according to NCI CTCAE Version 4.0
Time frame: 24 months
Psychological effects of treatment interruption
Time frame: 24 months
Evaluation of the reservoir replenishment by quantifying the viral reservoir under combined antiretroviral therapy (CART) in various anatomic compartments.(Total HIV DNA, integrated HIV DNA, Cell-associated-HIV RNA).
Time frame: 24 months
Evaluation of the reservoir replenishment by quantifying the viral reservoir under combined antiretroviral therapy (CART) in various anatomic compartments.(viral outgrowth assay).
Time frame: 24 months
Therapeutic drug monitoring assessed by drug concentrations measured in the different compartments
Time frame: 24 months
Assessment of the kinetics of HIV viral load rebound after treatment interruption based on the repetitive plasma viral load measurements.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2021.
- Derived from this study: PubMed 35476994Cole B, Lambrechts L, Boyer Z, Noppe Y, De Scheerder MA, Eden JS, Vrancken B, Schlub TE, McLaughlin S, Frenkel LM, Palmer S, Vandekerckhove L. Extensive characterization of HIV-1 reservoirs reveals links to plasma viremia before and during analytical treatment interruption. Cell Rep. 2022 Apr 26;39(4):110739. doi: 10.1016/j.celrep.2022.110739.
- Derived from this study: PubMed 32053203De Scheerder MA, Van Hecke C, Zetterberg H, Fuchs D, De Langhe N, Rutsaert S, Vrancken B, Trypsteen W, Noppe Y, Van Der Gucht B, Pelgrom J, Van Wanzeele F, Palmer S, Lemey P, Gisslen M, Vandekerckhove L. Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption. J Antimicrob Chemother. 2020 May 1;75(5):1311-1320. doi: 10.1093/jac/dkaa003.
- publicationLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linos Vandekerckhove, Prof principal investigator
UZ Gent - U Gent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing treatment interruption after in depth sampling under CART in people with HIV, run by University Hospital, Ghent at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02641756, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2021.