Reducing Systemic Inflammation in People on Antiretroviral Therapy

ConditionsHuman Immunodeficiency Virus (HIV)Cardiovascular Risk Factor

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorCentre hospitalier de l'Université de Montréal (CHUM)

About this trial

This randomized, open-label clinical trial will evaluate whether adding fostemsavir to current antiretroviral therapy can reduce the risk of cardiovascular disease in people with well-controlled HIV. Researchers will compare imaging, clinical and biomarker outcomes between participants who receive fostemsavir in addition to their existing treatment and those who continue with standard care alone.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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);

Trial design

Design model

Parallel

Treatments tested in this trial

Fostemsavir
Drug
Addition of fostemsavir to the patient's current antiretroviral regimen: once daily oral administration (Rukobia 600 mg extended-release tablets) for 24 months

Treatment groups

150 Participants

are divided into 2 treatment groups

Group A: Rukobia 600 mg dailyExperimental treatment 1 intervention

Group B: Standard of care (SOC)No intervention 0 interventions

Trial outcomes

Primary outcomes

Change in total uncalcified plaque volume between baseline and month 24

The change in total uncalcified plaque volume between baseline and month 24 will be measured by coronary compted tomography angiography and contrasted between fostemsavir and standard of care

Time frame

From baseline to end of treatment (+ 24 months)

Secondary outcomes

Imaging outcome: Perivascular fat attenuation index at month 24, adjusted for baseline values

The perivascular fat attenuation index at month 24, adjusted for baseline values, will be measured by CCTA and contrasted between fostemsavir and standard of care

Time frame

From baseline to end of treatment (+ 24 months)

Time to Major Adverse cardiovascular Event (MACE)

The time to MACE will be recorded throughout the study. MACEs are defined as myocardial infarction, coronary revascularization by percutaneous coronary intervention or surgery, peripheral artery revascularization, stroke, hospitalization for heart failure or unstable angina, or cardiovascular death

Time frame

From baseline to post-treatment visit (+ 27 months)

Risk of severe and serious adverse events

Time frame

From baseline to post-treatment visit (+ 27 months)

Grip strength at 24 months, adjusted for baseline

Grip strength, a marker of sarcopenia, will be measured at month 24, adjusted for baseline. Grip strength will be measured using the standard operating procedures common to the Canadian HIV and Aging Cohort Study (CHACS) and Women's Interagency HIV Study (WHIS).

Time frame

From baseline to end of treatment (+ 24 months)

Other outcomes

Biological biomarkers of inflammation and immune dysfunction

The analysis of biomarkers will be presented as evolution over time between the study groups. Following marker groups will be assessed: Biomarkers of systemic inflammation and biomarkers associated to CVD Immuno-serology Presence of HIV soluble gp120 Plasma fostemsavir concentration

Time frame

From screening (up to T0 - 6 months) to post-treatment visit (T0 + 27 months)