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Starting or Switching to an Integrase Inhibitor-Based Regimen Affects PTSD Symptoms in Women with HIV

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Abstract

As the use of Integrase inhibitor (INSTI)-class antiretroviral medications becomes more common to maintain long-term viral suppression, early reports suggest the potential for CNS side-effects when starting or switching to an INSTI-based regimen. In a population already at higher risk for developing mood and anxiety disorders, these drugs may have significant effects on PTSD scale symptom scores, particularly in women with HIV (WWH). A total of 551 participants were included after completing ≥ 1 WIHS study visits before and after starting/switching to an INSTI-based ART regimen. Of these, 14% were ART naïve, the remainder switched from primarily a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Using multivariable linear mixed effects models, we compared PTSD Civilian Checklist subscale scores before and after a “start/switch” to dolutegravir (DTG), raltegravir (RAL), or elvitegravir (EVG). Start/switch to EVG improved re-experiencing subscale symptoms (P’s < 0.05). Switching to EVG improved symptoms of avoidance (P = 0.01). Starting RAL improved arousal subscale symptoms (P = 0.03); however, switching to RAL worsened re-experiencing subscale symptoms (P < 0.005). Starting DTG worsened avoidance subscale symptoms (P = 0.03), whereas switching to DTG did not change subscale or overall PTSD symptoms (P’s > 0.08). In WWH, an EVG-based ART regimen is associated with improved PTSD symptoms, in both treatment naïve patients and those switching from other ART. While a RAL-based regimen was associated with better PTSD symptoms than in treatment naïve patients, switching onto a RAL-based regimen was associated with worse PTSD symptoms. DTG-based regimens either did not affect, or worsened symptoms, in both naïve and switch patients. Further studies are needed to determine mechanisms underlying differential effects of EVG, RAL and DTG on stress symptoms in WWH.

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Acknowledgements

This work was supported by the Johns Hopkins University NIMH Center for novel therapeutics for HIV-associated cognitive disorders (P30MH075773) 2018 pilot award to Dr. Rubin, a 2019 NSF grant (DMS- 1918854/ 1918851) to Drs. Xu and Rubin, and the Johns Hopkins University Center for AIDS Research NIH/NIAID fund (P30AI094189) 2019 faculty development award to Dr. Xu. Dr. Williams effort was supported by R00DA044838. Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH).WIHS (Principal Investigators): UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I—WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA).

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  1. Asante R. Kamkwalala, Kunbo Wang, Yanxun Xu and Leah H. Rubin have equally contributed to this work.

Authors and Affiliations

  1. Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/ Meyer 6-113, Baltimore, MD, 21287-7613, USA

    Asante R. Kamkwalala, Raha Dastgheyb, Kathryn C. Fitzgerald & Leah H. Rubin

  2. Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA

    Kunbo Wang

  3. Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA

    Jane O’Halloran & Yanxun Xu

  4. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Dionna W. Williams

  5. Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Dionna W. Williams

  6. Department of Medicine, Division of Infectious Disease and Travel Medicine, Georgetown University, Washington, DC, USA

    Amanda B. Spence

  7. Departments of Psychiatry, Psychology and OB/GYN, University of Illinois at Chicago, Chicago, IL, USA

    Pauline M. Maki

  8. Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA

    Deborah R. Gustafson

  9. Institute for Health Promotion & Disease Prevention Research, University of Southern California, Los Angeles, CA, USA

    Joel Milam

  10. Albert Einstein College of Medicine, Bronx, NY, USA

    Anjali Sharma

  11. CORE Center, Cook County Health and Hektoen Institute of Medicine, Chicago, IL, USA

    Kathleen M. Weber

  12. Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Adaora A. Adimora

  13. Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA, USA

    Igho Ofotokun, Anandi N. Sheth & Cecile D. Lahiri

  14. University of Miami Miller School of Medicine, Miami, FL, USA

    Margaret A. Fischl

  15. Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, MS, USA

    Deborah Konkle-Parker

  16. Division of Biostatistics and Bioinformatics at The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Yanxun Xu

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

    Leah H. Rubin

  18. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Leah H. Rubin

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  1. Asante R. Kamkwalala
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  20. Leah H. Rubin
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Correspondence to Leah H. Rubin.

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Kamkwalala, A.R., Wang, K., O’Halloran, J. et al. Starting or Switching to an Integrase Inhibitor-Based Regimen Affects PTSD Symptoms in Women with HIV. AIDS Behav 25, 225–236 (2021). https://doi.org/10.1007/s10461-020-02967-2

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