title: Persistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study.
abstract: Major depressive disorder is the most common neuropsychiatric complication in human immunodeficiency virus (HIV) infections and is associated with worse clinical outcomes. We determined if detectable cerebrospinal fluid (CSF) HIV ribonucleic acid (RNA) at threshold ≥50 copies/ml is associated with increased risk of depression. The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort is a six-center US-based prospective cohort with bi-annual follow-up of 674 participants. We fit linear mixed models (N = 233) and discrete-time survival models (N = 154; 832 observations) to evaluate trajectories of Beck Depression Inventory (BDI) II scores and the incidence of new-onset moderate-to-severe depressive symptoms (BDI ≥ 17) among participants on combination antiretroviral therapy (cART), who were free of depression at study entry and received a minimum of three CSF examinations over 2496 person-months follow-up. Detectable CSF HIV RNA (threshold ≥50 copies/ml) at any visit was associated with a 4.7-fold increase in new-onset depression at subsequent visits adjusted for plasma HIV RNA and treatment adherence; hazard ratio (HR) = 4.76, (95 % CI 1.58-14.3); P = 0.006. Depression (BDI) scores were 2.53 points higher (95 % CI 0.47-4.60; P = 0.02) over 6 months if CSF HIV RNA was detectable at a prior study visit in fully adjusted models including age, sex, race, education, plasma HIV RNA, duration and adherence of CART, and lifetime depression diagnosis by Diagnostic Statistical Manual (DSM-IV) criteria. Persistent CSF but not plasma HIV RNA is associated with an increased risk for new-onset depression. Further research evaluating the role of immune activation and inflammatory markers may improve our understanding of this association.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. ehammond@jhu.edu.|Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA. ehammond@jhu.edu.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Hammond
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Crum
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA.|Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Treisman
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.affiliation: Department of Neurology, Washington University, St. Louis, MO, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.affiliation: Department of Neurology, University of California, San Diego, CA, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: Department of Pathology, University of Texas, Medical Branch, Galveston, TX, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: Department of Psychiatry, University of California, San Diego, CA, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.affiliation: Department of Medicine, University of California, San Diego, CA, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.affiliation: Department of Neurology, University of Washington, Seattle, WA, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Departments of Neurology and Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Mcarthur
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D003863:Depression / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000523:psychology; D003865:Major Depressive Disorder / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000523:psychology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000523:psychology; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D012720:Severity of Illness Index
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D012367:RNA, Viral
keywords: Cerebrospinal fluid; Depression; Psychiatry; Viral load