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Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation

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Abstract

This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm3, t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann–Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.

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Notes

  1. As immune activation can be influenced by hormone changes, we completed sensitivity analyses removing from the dataset all cisgender women (n = 5), as well as transgender women (n = 3) who may have been taking hormone supplementation. We found no substantial differences in the reported outcomes. Significance was lost on correlation between baseline HADS-A anxiety score and CD4 count at baseline (p = 0.066, r = −0.17, n = 115) likely owing to a reduced sample size, as a trend towards significance remains. Additionally, all statistical models were re-run including sex as a covariate to examine any differential effect sex would have on the other covariates or the outcome. Sex was not a significant covariate in any of the models.

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Acknowledgements

We thank our study participants and staff from the Thai Red Cross AIDS Research Centre and the Silom Community Clinic in Bangkok, and the Early Capture HIV Cohort (ECHO) Center in Pattaya, Thailand for their valuable contributions to this study. RV254/SEARCH is a research collaboration between the Thai Red Cross AIDS Research Centre (TRCARC), the University of California San Francisco, the University of Hawaii, and the Department of Retrovirology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), and the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research. The SEARCH 010 Study Group also includes the following individuals: Praphan Phanuphak, M.D., Ph.D. (SEARCH, TRCARC, clinical investigator); Nittaya Phanuphak, M.D., Ph.D. (SEARCH, principal investigator); Eugene Kroon, M.D., MPH (SEARCH, clinical investigator); Carlos Secdalan, M.D. (SEARCH, clinical investigator); Nitiya Chomchey, MSc, (SEARCH, study coordinator); Somprartthana Rattanamanee, MSc (SEARCH, research nurse); Puttachard Sangtawan, BNS (SEARCH, research nurse); Bessara Nuntapinit, B.Sc. (AFRIMS, lead of specimen processing team); Phiromrat Rakyat, B.Sc. (AFRIMS, specimen processing); Surasit Inprakong, B.Sc. (AFRIMS, specimen processing); Sukanya Lucksanawong, B.Sc. (AFRIMS, specimen processing); Panjaree Ruangjan, MPH (AFRIMS, specimen processing); Anake Nuchwong, B.Sc. (AFRIMS, specimen processing); Panadda Kruacharoen, B.Sc. (AFRIMS, specimen processing); Robert O’Connell, M.D. (AFRIMS, clinical investigator); Collin Adams, BS (UCSF, study coordinator); Katherine Clifford, B.A. (UCSF, study coordinator); Leah Le, MPH (Yale University, study coordinator); Hetal Mistry, BS (Yale University, research associate); Sodsai Tovanabutra, Ph.D. (Military HIV Research Program, lab investigator); Suteeraporn Pinyakorn, MSc (Military HIV Research Program, statistician); Merlin Robb, M.D. (Military HIV Research Program, clinical investigator).

Funding

This study was funded by the National Institutes of Health (R01MH095613, R21MH086341, R01MH09561302-S1, R01NS061696) and the US Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, Maryland, under a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (W81XWH-07-2-0067), with added support from the National Institutes of Mental Health.

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Authors and Affiliations

  1. Department of Neurology, University of California, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA

    Joanna Hellmuth, Victor Valcour & Derek Ochi

  2. SEARCH, The Thai Red Cross AIDS Research Center, Bangkok, Thailand

    Donn Colby, Duanghathai Suttichom & Peeriya Prueksakaew

  3. Department of Neurology, Yale University, New Haven, CT, USA

    Serena Spudich

  4. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA

    Jintanat Ananworanich, Linda L. Jagodzinski & Bonnie Slike

  5. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA

    Jintanat Ananworanich & Bonnie Slike

  6. Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawaii, Honolulu, HI, USA

    Napapon Sailasuta

  7. Department of Epidemiology and Biostatistics, University of California, San Francisco, USA

    Isabel Allen

  8. Missouri Institute of Mental Health, University of Missouri-St. Louis, St. Louis, MO, USA

    Robert Paul

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  1. Joanna Hellmuth
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Consortia

on behalf of the RV254/SEARCH 010 Study Group

  • Praphan Phanuphak
  • , Nittaya Phanuphak
  • , Eugene Kroon
  • , Carlos Secdalan
  • , Nitiya Chomchey
  • , Somprartthana Rattanamanee
  • , Puttachard Sangtawan
  • , Bessara Nuntapinit
  • , Phiromrat Rakyat
  • , Surasit Inprakong
  • , Sukanya Lucksanawong
  • , Panjaree Ruangjan
  • , Anake Nuchwong
  • , Panadda Kruacharoen
  • , Robert O’Connell
  • , Collin Adams
  • , Katherine Clifford
  • , Leah Le
  • , Hetal Mistry
  • , Sodsai Tovanabutra
  • , Suteeraporn Pinyakorn
  •  & Merlin Robb

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Correspondence to Joanna Hellmuth.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Hellmuth, J., Colby, D., Valcour, V. et al. Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation. AIDS Behav 21, 3238–3246 (2017). https://doi.org/10.1007/s10461-017-1788-4

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