Integrase Inhibitors are Associated with Neuropsychiatric Symptoms in Women with HIV

Leah H. Rubin, Jane A. O’Halloran, Dionna W. Williams, Yuliang Li, Kathryn C. Fitzgerald, Raha Dastgheyb, Alexandra L. Damron, Pauline M. Maki, Amanda B. Spence, Anjali Sharma, Deborah R. Gustafson, Joel Milam, Kathleen M. Weber, Adaora A. Adimora, Igho Ofotokun, Margaret A. Fischl, Deborah Konkle-Parker, Yanxun Xu

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Women with HIV(WWH) are more likely to discontinue/change antiretroviral therapy(ART) due to side effects including neuropsychiatric symptoms. Efavirenz and integrase strand transfer inhibitors(INSTIs) are particularly concerning. We focused on these ART agents and neuropsychiatric symptoms in previously developed subgroups of WWH that differed on key sociodemographic factors as well as longitudinal behavioral and clinical profiles. WWH from the Women’s Interagency HIV Study were included if they had ART data available, completed the Perceived Stress Scale-10 and PTSD Checklist-Civilian. Questionnaires were completed biannually beginning in 2008 through 2016. To examine ART-symptom associations, constrained continuation ratio model via penalized maximum likelihood were fit within 5 subgroups of WWH. Data from 1882 WWH contributed a total of 4598 observations. 353 women were previously defined as primarily having well-controlled HIV with vascular comorbidities, 463 with legacy effects(CD4 nadir < 250cells/mL), 274 aged ≤ 45 with hepatitis, 453 between 35–55 years, and 339 with poorly-controlled HIV/substance users. INSTIs, but not efavirenz, were associated with symptoms among key subgroups of WWH. Among those with HIV legacy effects, dolutegravir and elvitegravir were associated with greater stress/anxiety and avoidance symptoms(P’s < 0.01); dolutegravir was also associated with greater re-experiencing symptoms(P = 0.005). Elvitegravir related to greater re-experiencing and hyperarousal among women with well-controlled HIV with vascular comorbidities(P’s < 0.022). Raltegravir was associated with less hyperarousal, but only among women aged ≤ 45 years(P = 0.001). The adverse neuropsychiatric effects of INSTIs do not appear to be consistent across all WWH. Key characteristics (e.g., age, hepatitis positivity) may need consideration to fully weight the risk–benefit ratio of dolutegravir and elvitegravir in WWH. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
JournalJournal of Neuroimmune Pharmacology
DOIs
StateAccepted/In press - 2022

Keywords

  • Antiretroviral
  • Heterogeneity
  • HIV
  • PTSD
  • Stress
  • Women

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