Depression Therapy to Improve Cardiovascular Risk in HIV

The objectives of this study will be met by performing a 24-week, randomized, controlled,
single-blinded, two-arm, parallel group, pilot trial at a single center. A total of 200
subjects may be screened to identify 110 participants to be enrolled and randomized. These
participants will be ≥ 18 years old, have been receiving antiretroviral therapy for at least
one year with an HIV viral load < 75 copies/mL at screening, and have major depression using
the PHQ-9 questionnaire. These participants will be randomized 1:1 to either depression
treatment with the Beating-the-Blues cognitive behavioral therapy program (N=55) or usual
care (N=55).

Inclusion Criteria:

- HIV-1 infection, documented by both: (1) any licensed rapid HIV test or HIV enzyme
test kit at any time prior to study entry and (2) by at least one detectable HIV-1
antigen or at least one detectable plasma HIV-1 RNA viral load

- Age equal to or greater than 18 years

- Receipt of antiretroviral therapy of any kind for at least 360 days prior to screening

Note: Interruptions in ART of up to 14 days total during the 360 days prior to screening
are allowed

- HIV-1 RNA level < 75 copies/mL at screening

NOTE: There are no CD4 cell count eligibility criteria for this trial

- For women who are still of reproductive potential, a negative urine pregnancy test

- Depression as defined by having a score ≥ 10 on the PHQ-9 questionnaire

Exclusion Criteria:

- Inability to complete written, informed consent

- Incarceration at the time of any study visit

- Active suicidality, as determined by the patient's HIV provider or social worker
following a positive response (1, 2, or 3) to PHQ-9 Item #9 and a positive response
(yes) to one or more of the three questions on the Patient Suicidality Form (with last
suicide attempt within the past ten years)

- Diagnosed vascular disease (documented history of angina pectoris, coronary disease,
peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise
known atherosclerotic disease)

- History of congestive heart failure, even if currently compensated

- Diagnosed disease or process, besides HIV infection, associated with increased
systemic inflammation (including, but not limited to, systemic lupus erythematosis,
inflammatory bowel diseases, other collagen vascular diseases)

Note: Hepatitis B or C co-infections are NOT exclusionary

- Known or suspected malignancy requiring systemic treatment within 180 days of
screening

NOTE: Localized treatment for skin cancers is not exclusionary

- History of Raynaud's phenomenon

- History of cardiac arrhythmias or cardiomyopathy

- Uncontrolled hyperthyroidism or hypothyroidism, defined as TSH values outside of the
local reference range on most recent clinical assessment

- History of carotid bruits

- Systolic blood pressure > 160 mmHg or diastolic blood pressure > 110 mmHg at screening

- Screening estimated glomerular filtration rate (eGFR) < 50 mL/min/1.732 (using the
2009 CKD-EPI equation) using a serum creatinine level measured at screening

- Screening glucose ≥ 140 mg/dL or hemoglobin A1c > 8.0%

- Screening total cholesterol > 240 mg/dL

- Therapy for serious medical illnesses within 14 days prior to screening

Note: Therapy for serious medical illnesses that overlaps with a main study visit will
result in postponement of that study visit until the course of therapy is completed;
postponement outside of the allowed study visit timeframe will result in study
discontinuation

- Pregnancy or breastfeeding during the course of the study

- Receipt of investigational agents, cytotoxic chemotherapy, systemic glucocorticoids
(of any dose), or anabolic steroids at screening

Note: Physiologic testosterone replacement therapy or topical steroids is not exclusionary.
Inhaled/nasal steroids are not exclusionary as long as the participant is not also
receiving HIV protease inhibitors

- Active drug use or dependence that, in the opinion of the investigator, would
interfere with adherence to study requirements

- History of schizophrenia or bipolar disorder