Clinical trial NCT02590354: Analytical Treatment Interruption in HIV Positive Patients
Official title: Analytical Treatment Interruption in HIV Positive Patients With Low Viral Reservoir to Evaluate the Potential of a Functional Cure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV-1 Infection
Keywords: Treatment interruption
functional cure
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: Universitair Ziekenhuis Brussel
name: Saint-Pierre University Hospital
name: Agentschap voor Innovatie door Wetenschap en Technologie
First posted: 2015-10-29
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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 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.


Eligibility criteria: Inclusion Criteria:

* 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
* 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).

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
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
timeFrame: 48 weeks after treatment interruption
Secondary outcomes:
measure: 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
timeFrame: 23 months
measure: 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).
timeFrame: At screening, baseline, week 2, week 4, week 6, week 8 and at 12 weeks after relapse
measure: 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).
timeFrame: At screening, baseline, week 2, week 4, week 6, week 8 and at 12 weeks after relapse
measure: Assessment of the Kinetics of HIV Viral Load Rebound After Treatment Interruption Based on the Repetitive Plasma Viral Load Measurements.
timeFrame: At screening, baseline, week 2, week 4, week 6, week 8, End of Intervention (relapse), 4 weeks after relapse and 12 weeks after relapse
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine
city: Brussels
country: Belgium
facility: Saint-Pierre University Hospital
city: Brussels
country: Belgium
facility: Brussels University Hospital
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: Institute of Tropical Medicine
name: Eric Florence, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.