HIV-1 InfectionISALANCT02590354
Analytical Treatment Interruption in HIV Positive Patients
A study testing ART interruption in people with HIV-1 Infection, run by Institute of Tropical Medicine, Belgium at 4 sites in Belgium.
Trial summary
HIV-1 infected patients with normal peripheral blood CD4+ T-cell counts and undetectable viral load will be recruited in four Belgian HIV reference centers. Selected patients will undergo a two-step screening in which a viral reservoir measurement will be performed and among those with a very low viral reservoir an… Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- ART interruption
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 4 sitesBelgium
- Study dates
- 25 Jan 2016to 22 Jun 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Able and willing to provide written informed consent
- Men and women age ≥ 18 and < 65 years.
- Confirmed HIV-1 infection at any time prior to study entry.
- Infected with HIV-1 subtype A, B, C, D, CRF01_AE or CRF02_AG virus
- Participant should take ART for at least 2 years before baseline with no changes in the ART regimen for at least 90 days prior to study entry. ART regimen is defined as mono- or bi-therapy or a combination of three or more active antiretroviral drugs
- CD4 T-cell count is >= 500/μl for a period of at least 3 months prior study entry
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- Nadir CD4+ T-cell count is ≥300/μl. A lower nadir CD4+ T-cell count will be allowed if measured at time of acute infection as far as the relative CD4+ count remains above 20%. An acute infection is defined as an association of a clinical picture of retroviral syndrome together with a seroconversion in HIV serology or an incomplete confirmation test.
- Plasma viral load < 50 copies/ml for at least 2 years before baseline. (Occasional "blips" will be permitted if it happened more than six months before study entry. An occasional 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).
- Willingness to complete scheduled assessments and participant visits.
- Adequate peripheral vein access to perform leukapheresis
- All female participants of childbearing potential should have a negative pregnancy test. These women and their partner should use double barrier contraception during the study. Females of reproductive potential will need a negative serum or urine pregnancy test at screening. They are defined as those who have not reached menopause or been post-menopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy or tubal ligation) . 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 a conception process (e.g., active attempt to become pregnant, sperm donation, or in vitro fertilization).
Who cannot join
- Previous or current history of AIDS defining event as defined in category C of the 'Centers for disease control and prevention (CDC)' clinical classification .
- Any acute infection or serious medical illness within 60 days prior to study entry. Participants will be excluded from this study for a serious illness (requiring systemic treatment and/or admission) until the subject either completes therapy or is clinically stable on therapy, in the opinion of the Investigator, for at least 14 days prior to study entry
- History of resistance to antiretroviral drugs, documented by genotyping.
- Active hepatitis B or C virus infection: as defined with a positive serology for either disease with signs of active viral replication?
- Significant risk of HIV transmission during treatment interruption in the opinion of the investigator. This includes evidence for unsafe sexual contacts.
- Current or past 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 MDRD equation) below 50 ml/min or the presence of HIV associated nephropathy 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 and breastfeeding.
- Any condition, including psychiatric and psychological disorders that might interfere with adherence to study requirements or safety of the participant.
- Prior use of any HIV vaccine and/or non-established experimental therapy
- Any of the following laboratory test results at screening: 1. Confirmed hemoglobin <11g/dl for women and <12 g//dl for men 2. Confirmed platelet count < 90,000/μl 3. Confirmed neutrophil count <1200/μl 4. Confirmed AST and/or ALT > 5 x upper limit on normal range (ULN). One retest within 14 days is allowed.
- Receipt of any immune modulator or suppressor within 30 days prior study entry, including, but not limited to drugs such as corticosteroids (with the exception of corticosteroids used for topical use), granulocyte-macrophage colony-stimulating factor, interleukin (IL)-2, IL-7 and IL-15.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Participation in other interventional studies involving investigational drug.
Trial locations and contacts
4 sites in 1 country.
Belgium4 sites
Institute of Tropical Medicine
Antwerp, 2000
Saint-Pierre University Hospital
Brussels, 1000
Brussels University Hospital
Brussels, 1090
Ghent University Hospital
Ghent, 9000
About this study
Official title: Analytical Treatment Interruption in HIV Positive Patients With Low Viral Reservoir to Evaluate the Potential of a Functional Cure
HIV-1 infected patients with normal peripheral blood CD4+ T-cell counts and undetectable viral load will be recruited in four Belgian HIV reference centers. Selected patients will undergo a two-step screening in which a viral reservoir measurement will be performed and among those with a very low viral reservoir an analytical treatment interruption of their longstanding antiretroviral therapy (ART). There is no randomization foreseen. Patients will receive an intense clinical and laboratory follow-up during 48 weeks followed by 12 weeks post intervention.
- Conditions
- HIV-1 Infection
- Being tested
- ART interruption
- Keywords
- Treatment interruption, functional cure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ART interruptionOther
| Study group | Role | What they receive |
|---|---|---|
| Treatment interruption | Experimental | The ART treatment in patients with a very low viral reservoir will be interrupted. Receives: Other: ART interruption |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the Number of Participants With a HIV Plasma Viral Load Below the Lower Limit of Detection 48 Weeks Following Interruption of Antiretroviral Treatment
The number of post treatment controllers (PTC - i.e. patients under ART at baseline that show low peripheral blood proviral DNA and still will show sustained viral suppression at 48 weeks after treatment interruption) will be determined. The assessment will be based on the plasma viral load (expressed in copies/ml) measured two-weekly (or four-weekly after W12) until W48 after treatment interruption. Patients below the lower limit of detection (<50 HIV RNA copies/ml plasma) at 48 weeks after treatment interruption will be considered as PTC.
Measured: 48 weeks after treatment interruption
Secondary outcomes (4)
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
Confirmation of the safety of a treatment interruption strategy in selected patients will be based on the number and intensity of AEs 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: 23 months
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA).
Assessment of the viral reservoir magnitude on cryopreserved Peripheral Blood Mononuclear Cells (PBMCs) prior and after treatment interruption by means of Total HIV DNA.
Measured: At screening, baseline, week 2, week 4, week 6, week 8 and at 12 weeks after relapse
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA).
Assessment of the viral reservoir magnitude on cryopreserved Peripheral Blood Mononuclear Cells (PBMCs) prior and after treatment interruption by means of unspliced RNA.
Measured: At screening, baseline, week 2, week 4, week 6, week 8 and at 12 weeks after relapse
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 (or four-weekly after W12) until W48 after treatment interruption. A viral load of 19 means <20 copies/mL (lower limit of detection).
Measured: At screening, baseline, week 2, week 4, week 6, week 8, End of Intervention (relapse), 4 weeks after relapse and 12 weeks after relapse
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2015 (estimated)
- Study start25 Jan 2016
- Primary completion22 Jun 2018
- Study completion22 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Tropical Medicine, Belgium
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Ghent, Universitair Ziekenhuis Brussel, Saint-Pierre University Hospital, Agentschap voor Innovatie door Wetenschap en Technologie
- Responsible party
- Sponsor
- Investigators
- Eric Florence, Dr, Principal investigator, Institute of Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02590354
- Sponsor's protocol ID
- ITM0714
- Acronym
- ISALA
- Status last verified
- Sep 2019
- First submitted
- 14 Oct 2015
- Last updated
- 24 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pannus P, Rutsaert S, De Wit S, Allard SD, Vanham G, Cole B, Nescoi C, Aerts J, De Spiegelaere W, Tsoumanis A, Couttenye MM, Herssens N, De Scheerder MA, Vandekerckhove L, Florence E. Rapid viral rebound after analytical treatment interruption in patients with very small HIV reservoir and minimal on-going viral transcription. J Int AIDS Soc. 2020 Feb;23(2):e25453. doi: 10.1002/jia2.25453.
PubMed 32107887
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analytical Treatment Interruption in HIV Positive Patients With Low Viral Reservoir to Evaluate the Potential of a Functional Cure
- ClinicalTrials.gov ID
- NCT02590354
- Acronym / sponsor ID
- ISALA / ITM0714
- Conditions
- HIV-1 Infection
- Keywords
- Treatment interruption, functional cure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Institute of Tropical Medicine, BelgiumUniversity, hospital or other
- Collaborators
- University Hospital, Ghent, Universitair Ziekenhuis Brussel, Saint-Pierre University Hospital, Agentschap voor Innovatie door Wetenschap en Technologie
- Study start
- 25 Jan 2016 (actual)
- Primary completion
- 22 Jun 2018 (actual)
- Study completion
- 22 Jun 2018 (actual)
- First posted
- 29 Oct 2015 (estimated)
- Results
- Posted 24 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HIV-1 infected patients with normal peripheral blood CD4+ T-cell counts and undetectable viral load will be recruited in four Belgian HIV reference centers. Selected patients will undergo a two-step screening in which a viral reservoir measurement will be performed and among those with a very low viral reservoir an analytical treatment interruption of their longstanding antiretroviral therapy (ART). There is no randomization foreseen. Patients will receive an intense clinical and laboratory follow-up during 48 weeks followed by 12 weeks post intervention.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment interruption | Experimental | Other: ART interruptionThe ART treatment in patients with a very low viral reservoir will be interrupted. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Able and willing to provide written informed consent
- Men and women age ≥ 18 and < 65 years.
- Confirmed HIV-1 infection at any time prior to study entry.
- Infected with HIV-1 subtype A, B, C, D, CRF01_AE or CRF02_AG virus
- Participant should take ART for at least 2 years before baseline with no changes in the ART regimen for at least 90 days prior to study entry. ART regimen is defined as mono- or bi-therapy or a combination of three or more active antiretroviral drugs
Key exclusion criteria (16 listed)
- Previous or current history of AIDS defining event as defined in category C of the 'Centers for disease control and prevention (CDC)' clinical classification .
- Any acute infection or serious medical illness within 60 days prior to study entry. Participants will be excluded from this study for a serious illness (requiring systemic treatment and/or admission) until the subject either completes therapy or is clinically stable on therapy, in the opinion of the Investigator, for at least 14 days prior to study entry
- History of resistance to antiretroviral drugs, documented by genotyping.
- Active hepatitis B or C virus infection: as defined with a positive serology for either disease with signs of active viral replication?
- Significant risk of HIV transmission during treatment interruption in the opinion of the investigator. This includes evidence for unsafe sexual contacts.
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 |
|---|---|---|
| ART interruption | Other | Treatment interruption |
Primary outcome
Assessment of the Number of Participants With a HIV Plasma Viral Load Below the Lower Limit of Detection 48 Weeks Following Interruption of Antiretroviral Treatment
Time frame: 48 weeks after treatment interruption
The number of post treatment controllers (PTC - i.e. patients under ART at baseline that show low peripheral blood proviral DNA and still will show sustained viral suppression at 48 weeks after treatment interruption) will be determined. The assessment will be based on the plasma viral load (expressed in copies/ml) measured two-weekly (or four-weekly after W12) until W48 after treatment interruption. Patients below the lower limit of detection (<50 HIV RNA copies/ml plasma) at 48 weeks after treatment interruption will be considered as PTC.
4 secondary outcomes
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: 23 months
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Total HIV DNA).
Time frame: At screening, baseline, week 2, week 4, week 6, week 8 and at 12 weeks after relapse
Evaluation of the Reservoir Replenishment Upon Interruption of Antiretroviral Treatment (TI) by Quantifying the Viral Reservoir at Baseline (i.e. Just Before TI) and at Viral Rebound (Unspliced RNA).
Time frame: At screening, baseline, week 2, week 4, week 6, week 8 and at 12 weeks after relapse
Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements.
Time frame: At screening, baseline, week 2, week 4, week 6, week 8, End of Intervention (relapse), 4 weeks after relapse and 12 weeks after relapse
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32107887Pannus P, Rutsaert S, De Wit S, Allard SD, Vanham G, Cole B, Nescoi C, Aerts J, De Spiegelaere W, Tsoumanis A, Couttenye MM, Herssens N, De Scheerder MA, Vandekerckhove L, Florence E. Rapid viral rebound after analytical treatment interruption in patients with very small HIV reservoir and minimal on-going viral transcription. J Int AIDS Soc. 2020 Feb;23(2):e25453. doi: 10.1002/jia2.25453.
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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.
Eric Florence, Dr principal investigator
Institute of Tropical Medicine
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ART interruption in people with HIV-1 Infection, run by Institute of Tropical Medicine, Belgium at 4 sites 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 11 inclusion and 16 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 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Yes. Results are posted in the registry (first posted 24 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Assessment of the Number of Participants With a HIV Plasma Viral Load Below the Lower Limit of Detection 48 Weeks Following Interruption of Antiretroviral Treatment (time frame: 48 weeks after treatment interruption). 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 NCT02590354, which also lists 1 linked publication.
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 24 Sep 2019.