SSRI Effects on Depression and Immunity in HIV/AIDS

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 18-64 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 40 copies/ml,

5. Current depressive symptoms (HAM-D-17 score equal or greater than 13), and a SCID
diagnosis of Major Depressive Disorder,

6. Able to understand and provide informed consent.

Exclusion Criteria:

1. Acute and marked suicidal ideation or intent,

2. Significant cognitive impairment or dementia,

3. Use of a medication known to alter immune function within 4 weeks prior to enrollment,

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,

9. History of bipolar disorder (I or II) or schizophrenia,

10. Current pharmacotherapy and/or psychotherapy 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. Taking diuretics,

14. History of seizures or taking Carbamazepine,

15. Taken MAOIs within 14 days,

16. On the antibiotic Linezolid and taking IV methylene blue,

17. On a regular regime of medication known to have anticoagulant properties such as
NSAID, aspirin or warfarin,

18. A history of acute narrow/closed angle glaucoma,

19. Currently taking CNS drugs,

20. On any triptan medications,

21. Undergoing ECT.