Reducing Systemic Inflammation in People on Antiretroviral Therapy

Inclusion criteria

• 40 years or older, or have lived with HIV for 25 years or more, any sex;
• Undetectable HIV viral load (defined as last viral load measurement less than 50 copies/ml within the last 6 months);
• Presence of at least one cardiovascular risk factor among the following: longstanding HIV infection (25 years or more), hypertension, diabetes, past or present smoking, dyslipidemia, family history of early onset CVD in a first-degree relative (defined as younger than 55 in males or younger than 65 in females (80)), known previous cardiovascular disease (defined as past myocardial infarction, coronary revascularization, stroke, or coronary artery atherosclerosis with \>= 50% stenosis demonstrated on coronary angiography or CCTA);
• Participants with past cardiovascular disease must be in a stable clinical condition as judged by the study clinicians;
• Past cardiovascular events are defined as having occurred at least 3 months before screening;
• Evidence of detectable plasmatic sgp120 levels at any point in the past year, using the assay described priorly and performed at CRCHUM in Dr Andrés Finzi's laboratory.

Exclusion criteria

• Known allergy to study drug;
• Concomitant treatment with strong cytochrome P450 (CYP3A) inducers, including but not limited to: carbamazepine, phenytoin (anticonvulsants), mitotane (antineoplastic), enzalutamide (androgen receptor inhibitor), rifampicin (antimycobacterial) and St John's wort (Hypericum perforatum, herbal supplement);
• Planning to become pregnant, pregnant, or breastfeeding (as requested per product monography (55)). Females of childbearing potential must have a negative pregnancy test at baseline visit, and follow contraception requirements throughout the treatment;
• Contraindication for CT scan use (estimated glomerular filtration rate \[eGFR\] less than 40ml/min using the Modification of Diet in Renal Diseases \[MDRD\] formula or iodine allergy);
• Elevated risk of prior ionizing radiation exposure outside clinical care exceeding 10 mSV over 3 years, per the investigator's judgement (eg. a participant with occupational ionizing radiation exposure, prior participation in clinical trials with multiple CT scans)
• Confirmed uncorrected QT value \>500ms or confirmed QTcF \>470 msec for women and \>450 msec for men;
• Acquired/ congenital long QT syndrome;
• Current or anticipated treatment with any of the following medications: amiodarone, disopyramide, dofetilide, ibutilide, procainamide, sotalol, and quinidine;
• Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy (INR \> 2.0), hypoalbuminemia (\<30 mg/ml), untreated esophageal or gastric varices, or persistently elevated bilirubinemia (\>1.5x upper limit of normal \[ULN\]), known biliary abnormalities (except Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment);
• ALT \>=5 times the ULN, OR ALT \>=3xULN and bilirubin \>=1.5xULN with \>35% direct bilirubin;
• History of liver cirrhosis with CHILD-PUGH classification C;
• Inability to provide informed consent;
• Life expectancy of less than 36 months;
• Inability to present to study visits;
• Participation in another interventional trial;
• Known Congestive heart failure with NYHA class 3 or 4.