Mitochondria in HIV and Aging (MITO+)

- Inclusion criteria:

- Between the ages of 50-75 years at study entry (a subset of participants changing
from TDF-based ART to TAF-based ART will also have mitochondrial function
measured and the age range for this subset is 18-70)

- Known HIV infection or presumed HIV uninfected (will be confirmed at screening)

- For HIV+ participants: must be on an ART regimen (change in regimen permitted for
preference/tolerability but not for virologic failure) for a minimum of 5 years,
with a viral load < 200 during the prior 2 years. The investigators will
initially target 10 years of therapy, but will expand to 5 years if needed for
enrollment.

- Although any ART regimen will be allowed if effective (as above), the
investigators will first target participants that have a history of > 5 years of
TDF exposure and are currently on TAF or TDF, but no prior exposure to AZT or
stavudine.

- CD4 T-cell count greater than 200 cells/mm3

- All participants must be able to perform activities of daily living without
assistance, and ambulate independently.

- Sedentary as defined above

- Post-menopausal as defined by cessation of menstrual periods for at least 12
months without any other obvious pathological or physiological cause OR removal
of ovaries at least 12 months prior to enrollment.

- Body mass index between 25-38 kg/m2

- Exclusion criteria:

- Participation in another clinical trial where the therapy is unknown or blinded.

- Diabetes, as defined by use of diabetes medications, hemoglobin A1c 6.5 or
greater, fasting plasma glucose 126 mg/dL or greater, or random plasma glucose
200 mg/dL or greater.

- Persons on statin therapy (as possible; this criteria may be removed for
recruitment difficulties).

- Fasting triglycerides > 400

- Untreated or incompletely treated thyroid disease will be excluded; stable
therapy for > 6 months will be allowed.

- Persons on growth hormone or growth hormone axis therapy (i.e., tesamorelin) will
be excluded.

- The investigators will initially target men, women, or transgendered individuals
without replacement hormone use. If the investigators are unable to recruit the
target number of participants, stable (>3 months) estrogen or testosterone within
physiologic replacement dose range will be permitted.

- Corticosteroid use, including intra-articular, will be excluded (within 3 months
for oral; within 6 months for intra-articular); inhaled or intranasal will be
permitted.

- Immunosuppressive medications within 6 months, including methotrexate,
infliximab, azathioprine, etc.

- Women that are pregnant, breast-feeding, or intend to become pregnant.

- Known hepatitis B or C with detectable viremia within in the past 6 months.

- Hepatitis C with undetectable viral load for at least 6 months will be allowed.

- Known mitochondrial disorder

- Severe liver disease other than hepatitis B or C due to interference with
systemic cytokine production

- Uncontrolled hypertension defined as resting systolic blood pressure (BP) >180
mmHg or diastolic BP >100 mmHg

- Indicators of unstable ischemic heart disease

- New York Heart Association Class III or IV congestive heart failure, clinically
significant aortic stenosis, uncontrolled angina, or uncontrolled arrhythmia

- Pulmonary disease requiring the use of supplemental oxygen

- Active malignancy (excluding non-melanoma skin cancers) within 24 weeks prior to
enrollment

- Surgery/trauma/injury/fracture within 12 weeks prior to enrollment that may limit
ability to perform physical function testing.

- Acute infection (skin infection, sinus infection, uncomplicated upper respiratory
infection, dental infection, etc) within 2 weeks of study entry will be excluded
until the infection has resolved for at least 2 weeks

- Chronic, deeper infections (complicated pneumonia, bone infection, liver abscess,
deep wound infection, etc) must have completed treatment and show no evidence of
ongoing infection for at least 12 weeks

- History of stroke with residual deficits

- Any medical condition that does not allow for a non-contrasted MRI study (ie,
pacemaker, shrapnel, other devices or hardware)

- AIDS-defining opportunistic infection75 within the 24 weeks prior to enrollment

- Severe anemia, defined as a hemoglobin of 9 mg/dL or less

- Participants on anticoagulants (clopidogrel, Coumadin, etc). Patients on
short-acting anticoagulant therapy requiring dose cessation for only 48-72 hours
can be considered for muscle biopsy with approval by their treating physician.

- Aspirin and Non-steroidal anti-inflammatory agents are not exclusions but should
be stopped 1 week prior to biopsy.