|Authors: Hammond ER, Crum RM, Treisman GJ, Mehta SH, Clifford DB, Ellis RJ, Gelman BB, Grant I, Letendre SL, Marra CM, Morgello S, Simpson DM, McArthur JC, for the CHARTER Group|
|Abstract:BACKGROUND: Major depressive disorder is the most common neuropsychiatric complication in persons with HIV and is associated with worse clinical outcomes. It is unknown whether detectable cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) ribonucleic acid (RNA) at thresholds ≥50 copies/ml, is associated with increased risk of new onset depression. We hypothesized a priori that detectable CSF HIV RNA is associated with increased risk of depressive symptoms and increasing depression scores.
METHODOLOGY: The CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort is a six center US based prospective cohort with bi annual follow up 674 participants. We fit linear mixed models (N=223) and discrete time survival models (N=154), a total of 832 observations, among participants on combination antiretroviral therapy (cART) enrolled from 2004 to 2007, and followed through 2009 over 2,496 person months. Participants were included in these analyses if they were free of depression at study entry and received a minimum of three CSF exams during follow-up. The main outcome measures were incidence of new onset moderate to severe depressive symptoms (BDI ≥17) and trajectories of BDI scores.
RESULTS: The mean age was 44.8 years, majority were male (81.6%), 44.8% Black, 39.5% White, and mean duration of current cART use was 18.1 months. At study entry, 32 (14.4%) participants had detectable CSF HIV RNA (≥50 copies/ml). Detectable CSF HIV RNA 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 to 14.3); P=0.006. BDI scores were 2.53 points higher (95% CI: 0.47 to 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 major depressive disorder by Diagnostic Statistical Manual of Mental Disorders, Fourth Edition criteria. Throughout follow up in adjusted linear mixed models, BDI scores for persons with detectable CSF HIV RNA increased, whereas BDI scores decreased when CSF HIV RNA was undetectable. Unlike the findings for CSF HIV RNA, plasma HIV RNA was not associated with an increase in BDI scores over time.
CONCLUSIONS: Persistent CSF but not plasma HIV RNA is associated with an increased risk for new-onset depression. Persons with persistent or worsening depression may benefit from CSF testing for HIV RNA, which may help guide HIV and depression treatment. Further research evaluating the role of immune activation and inflammatory markers will improve our understanding of this association. We speculate that depression may be a surrogate of ongoing CNS inflammation and injury.|