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

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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.

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Acknowledgments

The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) group is affiliated with the Johns Hopkins University, Mount Sinai School of Medicine, University of California, San Diego, University of Texas, Galveston, University of Washington, Seattle, Washington University, St. Louis and is headquartered at the University of California, San Diego and includes: Igor Grant, M.D. (UCSD, Director); Ronald J. Ellis, M.D., Ph.D. (UCSD, Co-Director); Scott L. Letendre, M.D. (UCSD, Co-Director); Ian Abramson, Ph.D. (UCSD, Co-Investigator); Muhammad Al-Lozi, M.D. (Washington University, Co-Investigator); J. Hampton Atkinson, M.D.(UCSD, Co-Investigator); Edmund Capparelli, Pharm.D. (UCSD, Co-Investigator); David Clifford, M.D. (Washington University, Site PI); Ann Collier, M.D. (University of Washington, Site Co-PI); Christine Fennema-Notestine, Ph.D. (UCSD, Core PI); Anthony C. Gamst, Ph.D. (UCSD, Core PI); Benjamin Gelman, M.D., Ph.D. (University of Texas, Site PI); Robert K. Heaton, Ph.D. (UCSD); Thomas D. Marcotte, Ph.D. (UCSD, Core PI); Christina Marra, M.D. (University of Washington, Site Co-PI); J. Allen McCutchan, M.D. (UCSD, Site PI); Justin McArthur, M.D. (Johns Hopkins, Site PI); Susan Morgello, M.D. (Mount Sinai, Site Co-PI); David M. Simpson, M.D. (Mount Sinai, Site Co-PI); Davey M. Smith, M.D. (UCSD, Core PI); Michael J. Taylor, Ph.D. (UCSD, Core Co-Investigator); Rebecca Theilmann, Ph.D. (UCSD, Imaging Physicist); Florin Vaida, Ph.D. (UCSD, Co-Investigator); Steven Paul Woods, Psy.D.(UCSD, Co-Investigator); Study coordinators: Terry Alexander, R.N. (UCSD, Neuromedical Coordinator); Clint Cushman (UCSD, Data Manager); Matthew Dawson (UCSD, Neurobehavioral Coordinator); Donald Franklin, Jr. (UCSD, Center Manager); Eleanor Head, R.N., B.S.N. (University of Texas, Site Coordinator); Trudy Jones, M.N., A.R.N.P. (University of Washington, Site Coordinator); Jennifer Marquie-Beck, M.P.H (UCSD, Recruitment Coordinator); Letty Mintz, N.P. (Mount Sinai, Site Coordinator); Vincent Rogalski, C.C.R.P (Johns Hopkins, Site Coordinator); Mengesha Teshome, M.D. (Washington University, Site Coordinator); and Will Toperoff, B.S., N.D. (UCSD, Site Coordinator).

The views expressed in this article are those of the authors and do not reflect the official policy or position of the US Government.

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Edward R. Hammond, Rosa M. Crum, Shruti H. Mehta & Justin C. Mcarthur

  2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD, 21287, USA

    Edward R. Hammond, Rosa M. Crum & Glenn J. Treisman

  3. Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Glenn J. Treisman & Justin C. Mcarthur

  4. Department of Neurology, Washington University, St. Louis, MO, USA

    David B. Clifford

  5. Department of Neurology, University of California, San Diego, CA, USA

    Ronald J. Ellis

  6. Department of Pathology, University of Texas, Medical Branch, Galveston, TX, USA

    Benjamin B. Gelman

  7. Department of Psychiatry, University of California, San Diego, CA, USA

    Igor Grant

  8. Department of Medicine, University of California, San Diego, CA, USA

    Scott L. Letendre

  9. Department of Neurology, University of Washington, Seattle, WA, USA

    Christina M. Marra

  10. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Susan Morgello & David M. Simpson

  11. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Susan Morgello

  12. Departments of Neurology and Pathology, Johns Hopkins University, Baltimore, MD, USA

    Justin C. Mcarthur

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for the CHARTER Group

Corresponding author

Correspondence to Edward R. Hammond.

Ethics declarations

The study was approved by the Institutional Review Board (IRB) or Western IRB for each study site and each participant provided written informed consent.

Funding

The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) is supported by the awards N01 MH22005, HHSN271201000027C, and HHSN271201000030C from the National Institutes of Health. The current analyses were funded by R03 MH095640-02 from the National Institutes of Mental Health. The study sponsor had no role in the design, analyses, interpretation, or reporting of the study.

Conflict of interest

Rosa M. Crum declares no conflict of interest. Ronald J. Ellis declares no conflict of interest. Igor Grant declares no conflict of interest. Benjamin B. Gelman declares no conflict of interest. Edward R. Hammond declares no conflict of interest. Justin C. McArthur declares no conflict of interest. David B. Clifford has been a Consultant to Biogen Idec, M.illennium, Bristol Myers Squibb, Pfizer, Genzyme, Amgen, Quintiles, and Sun Biopharma. Scott L. Letendre has research grants/grants pending from Abbvie, GlaxoSmithKline, and Merck. Christina M. Marra has received payment for lectures from universities and societies, and royalties from LLW, UpToDate. Shruti H. Mehta has received payment for lectures at a university. Susan Morgello has lectured for Health Clear Strategies. David M. Simpson has been a Consultant for Astellas, Merz, Ipsen, Acorda Therapeutics, Depomed, Syntaxin, Viromed, Biogen, and Allergan. Glenn J. Treisman has received payment for lectures from universities.

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Hammond, E.R., Crum, R.M., Treisman, G.J. et al. Persistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study. J. Neurovirol. 22, 479–487 (2016). https://doi.org/10.1007/s13365-015-0416-1

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  • DOI: https://doi.org/10.1007/s13365-015-0416-1

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