| Eligibility |
Inclusion Criteria:
- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or
chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and
confirmed by a licensed Western blot or a second antibody test by a method other than
the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load
OR two HIV-1 RNA >1,000 copies/mL.
- NOTE: The term "licensed" refers to a US Food and Drug Administration
(FDA)-approved kit, which is required for all investigational new drug (IND)
studies.
- WHO (World Health Organization) and CDC (Centers for Disease Control and
Prevention) guidelines mandate that confirmation of the initial test result must
use a test that is different from the one used for the initial assessment. A
reactive initial rapid test should be confirmed by either another type of rapid
assay or an E/CIA that is based on a different antigen preparation and/or
different test principle (e.g., indirect versus competitive), or a Western blot
or a plasma HIV-1 RNA viral load.
- Currently on a stable, continuous non-nucleoside reverse transcriptase inhibitor
(NNRTI)-based or unboosted integrase strand transfer inhibitor (INSTI)-based
antiretroviral therapy (ART) regimen for =48 weeks prior to study entry with no ART
interruption longer than 7 consecutive days and with no plans to change ART during the
course of the study.
- NOTE A: Stable is defined as no within-class changes in ART regimen within 12
weeks prior to study entry and no between-class changes for 24 weeks prior to
study entry.
- NOTE B: Unboosted ART is defined as an ART regimen that does not include the
pharmacologic booster COBI or RTV.
- NOTE C: Modifications of ART formulation within 12 weeks prior to study entry
(e.g., from standard formulation to fixed-dose combination of the same drugs),
are permitted.
- Screening HIV-1 RNA level below the limit of quantification (e.g., <20, <40, <50, or
<75 copies/mL, depending on the assay) using an FDA-approved assay with a
quantification limit of 75 copies/mL or lower performed by any laboratory that has a
Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent
within 90 days prior to study entry.
- All HIV-1 RNA levels within 48 weeks prior to study entry below the limit of
quantification (e.g., <20, <40, <50, or <75 copies/mL, depending on the assay) using
an FDA-approved assay with a quantification limit of 75 copies/mL or lower performed
by any laboratory that has a CLIA certification or its equivalent.
- NOTE A: Up to two HIV-1 RNA determinations that are between the assay
quantification limit and 500 copies/mL (i.e., "blips") are allowed as long as the
preceding and subsequent determinations are below the level of quantification.
- NOTE B: The screening value may serve as the subsequent undetectable value
following a blip.
- CD4+ cell count >200 cells/mm^3 obtained within 90 days prior to study entry at any US
laboratory that has a CLIA certification or its equivalent.
- At least one of the following cardiovascular risk factors (current diagnosis or
receiving treatment, except where a time period is specified):
- Clinical atherosclerotic disease (symptomatic atherosclerotic lesions in any
vessel)
- Subclinical atherosclerotic disease (coronary artery calcification [CAC] >10 or
presence of non-obstructive plaques)
- DM or prediabetes (hemoglobin A1c [HbA1c] =5.7%) or impaired fasting glucose
(documented fasting glucose of >100 mg/dL within 6 months prior to study entry)
or insulin resistance (HOMA-IR =2.6) or any one of these laboratory values within
6 months prior to study entry
- Obesity (body mass index [BMI] =30 kg/m^2) or enlarged iliac waist circumference
(>40 inches in males, >35 inches in females)
- NOTE: A BMI calculator is available at the Data Management Center (DMC) website:
https://www.fstrf.org/ACTG/ccc.html
- History of hypertension or blood pressure =130/80 mmHg measured during screening
- NOTE: Blood pressure should be measured following the current ACTG Standardized
Blood Pressure Measurement standard operating procedure (SOP). See the A5363
Manual of Procedures (MOPS) for the link to the SOP.
- Elevated LDL cholesterol (fasting LDL of >160 mg/dL; result from sample taken
within 90 days prior to study entry can be used)
- Low HDL cholesterol (<40 mg/dL; result from sample taken within 90 days prior to
study entry can be used)
- Smoking (any current tobacco smoking)
- Family history of premature CAD (first degree relative with CAD prior to age 55
for male relative and 65 for female relative; participant report is acceptable)
- hsCRP >2.0 mg/L within 90 days prior to study entry without an active infection
or acute illness at the time the sample was obtained
- The following laboratory values obtained within 90 days prior to study entry by any
laboratory that has a CLIA certification or its equivalent.
- Absolute neutrophil count (ANC) >750/mm^3
- Platelet count >100,000/mm^3
- Aspartate aminotransferase (AST) (SGOT) =5x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) (SGPT) =5x ULN
- Alkaline phosphatase =5x ULN
- Estimated glomerular filtration rate (GFR) =60 mL/min/1.73 m^2 as calculated
using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation
- NOTE: See the A5363 MOPS for further information and a link to the CKD-Epi
equation and calculator.
- Pre-entry FDG-PET/CT imaging (within 60 days prior to study entry) that has been
deemed:
- Interpretable as assessed by the central imaging core laboratory AND
- Without incidental findings that will preclude participation in the study at the
discretion of the site investigator
- For females of reproductive potential, negative serum or urine pregnancy test within
90 days prior to study entry and prior to starting study treatment at study entry by
any clinic or laboratory that has a CLIA certification or its equivalent, or is using
a point of care (POC)/CLIA-waived test.
- NOTE: Reproductive potential is defined as girls who have reached menarche and
women who have not been post-menopausal for at least 12 consecutive months with
follicle-stimulating hormone (FSH) =40 IU/mL or 24 consecutive months if an FSH
is not available, or have not undergone surgical sterilization (e.g.,
hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy).
- If participating in sexual activity that could lead to pregnancy, willingness of
female participants to use two forms of contraception while receiving study medication
and for 3 months after stopping study medication as required.
- NOTE A: Acceptable forms of contraception include:
- barrier methods (condoms [male or female] with or without a spermicidal agent,
diaphragm, or cervical cap [with spermicide])
- hormone-based contraception (oral, patch, parenteral, implants, or vaginal ring)
- intrauterine device (IUD)
- NOTE B: If the female participant is not of reproductive potential (women who are
post-menopausal as defined above, or women who have undergone surgical
sterilization [e.g., hysterectomy, bilateral oophorectomy, tubal ligation or
salpingectomy]), she is eligible without requiring the use of a contraceptive
method. Acceptable documentation of surgical sterilization and menopause is by
participant-reported history.
- Men and women age =45 years.
- Ability and willingness of participant or legal guardian/representative to provide
informed consent.
Exclusion Criteria:
- Acute coronary syndrome, defined as myocardial infarction (MI) or unstable angina,
within 90 days prior to study entry.
- A current diagnosis of latent or active tuberculosis (TB) infection, any prior
untreated TB infection, inadequate treatment of active TB, or inadequate treatment of
latent TB.
- NOTE A: Individuals with cases of active infection and latent TB infection with a
history of adequate treatment may be considered for enrollment provided the
individual has a negative chest X-ray following treatment and within 1 year prior
to study entry.
- NOTE B: Written documentation of prior TB treatment and negative chest x-ray is
required.
- Current diagnosis with other intracellular pathogens (Mycobacterium avium complex,
Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus neoformans) within 90 days
prior to study entry.
- Untreated hepatitis B virus (HBV) infection with detectable HBV DNA within 6 months
prior to study entry.
- Current hepatitis C virus (HCV) infection (i.e., detectable HCV RNA within 6 months
prior to study entry).
- Acute or clinically significant infection or illness requiring IV antibiotics or
hospitalization within 90 days prior to study entry.
- History of cirrhosis with severe hepatic impairment and/or hepatic decompensation
including ascites, hepatic encephalopathy, or variceal bleeding.
- Prior or planned liver transplantation.
- Active malignancy, except squamous cell skin cancer
- More than two HIV-1 RNA determinations =500 copies/mL within 48 weeks prior to study
entry.
- Hemoglobin A1c >8% within 90 days prior to study entry by any laboratory that has a
CLIA certification or its equivalent.
- Initiation of statin therapy or change in statin dose within 90 days prior to study
entry.
- Current use of any of the statins at the doses indicated:
- Atorvastatin, >20 mg/day dose
- Lovastatin, >40 mg/day dose
- Pitavastatin, >4 mg/day dose
- Pravastatin, >40 mg/day dose
- Rosuvastatin, =20 mg/day dose
- Simvastatin, >40 mg/day dose
- Anticipated addition of any lipid lowering medication during the course of the study.
- Concurrent use of drugs with potential drug-drug interactions with CVC within 90 days
prior to study entry (refer to the prohibited medications list in the study protocol).
- Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or
their formulation.
- Treatment within 30 days prior to study entry or anticipated treatment with
immunomodulating agents (such as systemic corticosteroids, interleukins, interferons,
cyclosporine, and tacrolimus).
- Immunization within 30 days prior to the pre-entry FDG-PET/CT imaging (refer to study
protocol).
- History of radiation therapy.
- High radiation exposure within one year prior to entry, defined as having undergone
more than two of any of the procedures below (includes having undergone the same
procedure twice within one year prior to study entry):
- Coronary artery catheterization with or without percutaneous coronary
intervention (PCI)
- Myocardial perfusion stress test
- Coronary CT angiography
- CT of the chest and abdomen
- Barium enema
- Currently pregnant, breastfeeding, or planning to become pregnant during the length of
the study and three months after completing the study.
- Body weight >300 pounds or >136 kilograms.
- Active drug or alcohol use or dependence that, in the opinion of the site
investigator, would interfere with adherence to study requirements.
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