perinatally HIV infection MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: ODEFSEY - 200 MG/25 MG/25 MG- COMPRESSA RIVESTITA- USO ORALE- FLACONE (HDPE) 30 COMPRESSE
Product Name: ODEFSEY
Product Code: [na]
Pharmaceutical Form: Film-coated tablet
INN or Proposed I
Sponsors
IRCCS, OSPEDALE PEDIATRICO BAMBINO GESÙ DI ROMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ITACO Inclusion Criteria 1. Males and females = 12 years old 2. HIV-1 infection 3. Written informed consent by adult patients or caregivers 4. Laboratory values at screening that meet the following criteria: a. Hemoglobin > 11.5 g/dL b. Absolute neutrophil count = 1000/mm3 c. Platelet count = 100,000/mm3 ITACO-ATI: 1. Subjects who completed ITACO path 2. Males and females =12 years old 3. Written informed consent by adult patients or caregivers 4. Subjects currently on the same regimen of 3 or more antiretroviral drugs for at least 1 year. 5. Evaluation of intact proviruses explored in the ITACO study within 24 months prior to Visit 1 revealing absence of intact proviruses isolated from at least 20 million peripheral blood mononuclear cells (PBMCs) or intact proviruses which are located in heterochromatin positions, which include (i) all non-genic positions, (ii) positions in ZNF genes on chromosome 19, which display extensive binding to heterochromatin proteins and are associated with repressive histone modifications. Testing for chromosomal locations of intact proviruses will be performed using an established assay termed MIP-Seq (matched integration site and proviral sequencing). 6. CD4+ cell count =200 cells/mm3 at study entry. 7. One documented plasma HIV-1 RNA that is below the limit of detection of an FDA-approved assay between 12 and 24 months prior to the screening HIV-1 RNA and one documented HIV-RNA that is below the limit of detection of an FDA-approved assay collected fewer than 12 months prior to the screening HIV-1 RNA. 8. Willingness to interrupt ART from the patient if an adult or both caregiver and adolescents Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 31 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: ITACO: 1. History of advanced coronary artery disease, myocardial infarction, severe Chronic obstructive pulmonary disease, chronic renal failure, decompensated cirrhosis, seizure disorder, or any other condition that in the opinion of the investigator will compromise ability to participate in the study. 2. Subject taking any of the following medications: systemic steroids (inhaled, nasal, or topical steroid therapy is permitted), interleukins, systemic interferons (e.g. local injection of interferon alpha or use of topical immune modulators for the treatment of HPV is permitted) or systemic chemotherapy. 3. Use of any immunomodulatory agents within 30 days prior to the study procedure. 4. Antibiotic use within 1 week of study procedures. 5. Recipient of a live vaccine within 2 weeks of study procedures. 6. Unwilling or unable to comply with study visit requirements. 7. Patients weighting 1000 copies/ml (at least 1 month apart) 4. Most recent two CD4% 1.5 times the upper limit of normal. 7. Currently breastfeeding or plans on breastfeeding during the course of the study or is pregnant. 8. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. 9. Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 60 days prior to entry. 10. Receipt of any study-defined prohibited medication within 6 months prior to entry (see point 4 of paragraph 3.7.2). 11. Significant pre-existing resistance to protease inhibitors and integrase inhibitors based on a review of pre-existing antiretroviral drug resistance testing data - according to the Stanford University HIV drug resistance database https://hivdb.stanford.edu/ 12. Latent hepatitis B infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ITACO AIMS: Quantify the susceptibility of the proviral reservoir to reactivation through the establishment of a predictive platform to early-select promising immune-targeted strategies to reverse HIV-1 latency in perinatal infection. 2.To select patients within the ITACO cohort according to the predictive platform (PredictHIV) built by data source obtained by aim 1), to be eligible for analytical antiretroviral treatment interruption (ITACO-ATI) ITACO-ATI AIMS: 1.Determine whether chromosomal integration of intact HIV-1 proviruses in repressive chromatin regions, obtained by the analysis produced in ITACO analysis, predicts delayed viral rebound during an ATI. 2.To evaluate changes in intact proviral reservoir configuration during ATI and after re-initiation of ART. 3.To evaluate innate and adaptive immune cell frequency and function during ATI and their association with the viral reservoir and viral rebound kinetics.;Secondary Objective: NA;Primary end point(s): 1.ITACO cohort: Proportion of patients with HIV intact proviruses, isolated from at least 20 million peripheral blood mononuclear cells (PBMCs), located in heterochromatin positions, which include (i) all non-genic positions, (ii) positions in ZNF genes on chromosome 19, which display extensive binding to heterochromatin proteins and associated with repressive histone modifications (PredictHIV negative) 2.ITACO-ATI cohort: Proportion of patients “PredictHIV negative” who underwent ATI without HIV RNA rebound ( = 1,000 copies/mL) at 6 months after ART discontinuation;Timepoint(s) of evaluation of this end point: ITACO: 24 weeks ITACO-ATI: 6 months after ART discontinuation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. ITACO cohort: • Proportion of patients with virus inducibility (TILDA assay) in the whole cohort and with distinct latency reversal agents (LRAs) in vitro • Proportion of patients with GALT with absence of intact HIV provirus • Adverse events and serious adverse events 2. ITACO-ATI cohort: • Time from ART discontinuation (start of ATI) to HIV RNA rebound to = 1,000 copies/mL. • Time from ART discontinuation to meeting criteria for ART re-initiation. • Proteomic and In Vitro Gene Expression Testing (IVIGET) associated to patients with viral rebound after ART discontinuation after 6 months compared to patients with viral rebound before 6 months from ART discontinuation. • CD4% • Adverse events and serious adverse events;Timepoint(s) of evaluation of this end point: ITACO: 24 weeks ITACO-ATI: at ART discontinuation and at 6 months after ART discontinuation | — |
Countries
Italy
Contacts
Public ContactUOC Immunologia Clinica e Vaccinolo
IRCCS Ospedale Pediatrico Bambino Gesù
Outcome results
None listed