This is a 10 week, double-blind, placebo controlled trial to evaluate SSRI (Selective Serotonin Reuptake Inhibitor) effects for treatment of depression in HIV/AIDS with a focus on innate immunity and inflammation. Depressed population is HIV + on cART (Combination Antiretroviral Therapy), not currently on pharmacotherapy for depression. Subjects will complete computerized cognitive behavior therapy, CCBT for their depression. Blood samples collected for virologic, neuroendocrine, and immunologic evaluation. Our overarching hypothesis is that SSRI treatment of depression and improvement of depressive symptoms leads to increased innate immunity and decreased inflammation, resulting in better control of HIV disease and decreased morbidity.

To pursue our long-term objective of successfully treating co-morbid mental and medical disorders in HIV/AIDS, this study aims to determine whether: 1) SSRI treatment significantly increases innate immunity and decreases chronic inflammation and immune activation, and 2) changes in depressive symptoms correlate with changes in immunity in HIV/AIDS.

HIV-seropositive, depressed subjects will be randomized to 10 weeks of double blind therapy with either escitalopram or placebo. All participants will concurrently begin CCBT (Computerized Cognitive Behavioral Therapy) using the program Good Days Ahead.

Subject visits will occur weekly for the first 6 weeks and then at weeks 8 and 10. The treating clinician will assess side effects, review symptomatic progress, and adjust the study medication as clinically appropriate. An independent clinical evaluator will assess patients at baseline, and weeks 1-6, 8 and 10. Blood samples collected at baseline and weeks 2, 4, and 10 will be used to assay markers of innate immune suppression (lytic units of NK cells, LUNK, and intracellular IFN gamma in NK cells) and markers of inflammation (IL-6 and C-Reactive Protein). At the end of the 10-week treatment phase, all participants will be referred for appropriate clinical treatment of their depression.

Inclusion Criteria:

1. Men and women aged 18-70 years, of any race and ethnicity,
2. HIV-seropositive by ELISA and Western Blot assays, infected by behavioral transmission (perinatal HIV excluded),
3. Willing and able to comply with antidepressant medication regimen and scheduled follow-up visits,
4. Currently on a documented regimen of cART for at least 3 months and Viral load less than 200 copies/ml,
5. Current depressive symptoms (HAM-D-17 score ≥ 13 and a SCID diagnosis of either Major Depressive Disorder, Persistent Depressive Disorder (Dysthymia), Unspecified Depressive Disorder, or Other Specified Depressive Disorder)
6. Able to understand and provide informed consent.

Exclusion Criteria:

1. Acute suicidal ideation, gestures, or attempts (e.g., HAM-D suicide item score of 3 "Ideas or gestures of suicide" or 4 "Attempts at suicide" at intake or HAM-D suicide item score of 4 "Attempts at suicide" during study),
2. Significant cognitive impairment or dementia including HIV Associated Dementia (HAD),
3. Use of a medication known to alter immune function within 4 weeks prior to randomization (the following are not excluded: a. acyclovir and related antiviral medications, b. topical corticosteroids, c. corticosteroid nasal sprays or inhalers, d) statin medications,),
4. Immunization with HIV vaccine,
5. Presence of psychotic symptoms or known diagnosis of a primary psychotic disorder,
6. Currently taking an anti-psychotic medication,
7. Pregnant or within nine months post-delivery, lactation,
8. Current or chronic medical condition that would likely preclude adherence to protocol or completion of the trial (per investigator judgment),
9. Bipolar disorder (I or II) or schizophrenia,
10. Current pharmacotherapy for treatment of depression,
11. A history of intolerance or nonresponse to an adequate trial of escitalopram (or other SSRIs),
12. Renal failure, including those who require dialysis,
13. History of epilepsy or seizure disorder,
14. Taken MAOIs within 14 days,
15. On the antibiotic Linezolid and taking IV methylene blue,
16. On a regular regime of medication known to have anticoagulant properties such as NSAID, aspirin or warfarin,
17. A history of acute narrow/closed angle glaucoma,
18. Currently taking CNS drugs (the following are not excluded: gabapentin, pregabalin, varenicline, antihistamines, and hypnotics (e.g. zolpidem, zaleplon, eszopiclone),
19. On any triptan medications,
20. Undergoing ECT.

10 weeks