Persistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study.

TitlePersistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study.
Publication TypeJournal Article
Year of Publication2016
AuthorsHammond, ER, Crum, RM, Treisman, GJ, Mehta, SH, Clifford, DB, Ellis, RJ, Gelman, B, Grant, I, Letendre, S, Marra, CM, Morgello, S, Simpson, DM, McArthur, JC
Corporate AuthorsCHARTER Group
JournalJ Neurovirol
Volume22
Issue4
Pagination479-87
Date Published2016 08
ISSN1538-2443
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Biomarkers, CHARTER, Depression, Depressive Disorder, Major, Female, HIV Infections, Humans, Internal, Male, Medication Adherence, Middle Aged, Prognosis, Prospective Studies, RNA, Viral, Severity of Illness Index
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.

DOI10.1007/s13365-015-0416-1
Alternate JournalJ. Neurovirol.
PubMed ID26727907
PubMed Central IDPMC4925276
Grant ListK24 MH097673 / MH / NIMH NIH HHS / United States
HHSN271201000030C / MH / NIMH NIH HHS / United States
HHSN271201000027C / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
R01 MH107345 / MH / NIMH NIH HHS / United States
R25 MH080661 / MH / NIMH NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States
R03 MH095640 / MH / NIMH NIH HHS / United States