This trial will determine if depression treatment will reduce cardiovascular risk in HIV-infected patients already receiving HIV treatments. Half of the participants will undergo a specific computerized depression treatment with the other half receiving usual care from their HIV providers.

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

6 months