The Italian Cohort (ITACO) and the Analytical Antiretroviral Treatment Interruption Italian Cohort (ITACO-ATI) study guided by molecular HIV-1 reservoir profiling

Lab values

• ITACO eligibility criteria Exclusion Criteria 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 <35kg. 8. Female subject who is pregnant as determined by urine pregnancy test or less than eight weeks post partum NOTE: Critical values to be considered for chronic renal failure are estimated glomerular filtration rate (eGFR) < or = 59mL/min/1,73m2. Chemistry values to be considered for decompensated cirrhosis are AST > 5 or /and ALT > 5 times the upper limit.
• ITACO-ATI eligibility criteria Exclusion criteria 1. Cannot or unwilling to attend visits required for the study 2. Unwilling to restart antiretroviral treatment (ART) if CD4 percent or count indicates this is necessary 3. Most recent two plasma HIV-1 RNA viral load > 1000 copies/ml (at least 1 month apart) 4. Most recent two CD4% <20% (at least 1 month apart) 5. 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. 6. S-Creatinine >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. Note: If a patient is hepatitis B core antibody-positive, s/he must be both hepatitis B surface antigen AND hepatitis B DNA negative. If a patient is hepatitis B core antibody negative, s/he must also be hepatitis B surface antigen negative. Critical values to be considered for chronic renal failure are estimated glomerular filtration rate (eGFR) < or = 59mL/min/1,73m2. Chemistry values to be considered for decompensated cirrhosis are AST > 5 or /and ALT > 5 times the upper limit.

• ITACO eligibility criteria 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 eligibility criteria Inclusion criteria 1. Subjects who completed ITACO 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 ITACO 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 NOTE: These participants will be counseled again regarding the requirement to use barrier protection for all sexual exposures while on study.