Antiretroviral Therapy and Neurocognitive Functions in People Living with HIV

  • Author / Creator
    Amusan, Precious
  • Despite the wide-spread availability of modern, combination antiretroviral therapy (cART), neurocognitive impairment persists among some people living with HIV (PWH). Among the multiple, interrelated HIV-associated, comorbid, and demographic factors related to neurocognitive problems in HIV today are also potential negative effects of cART (Nightingale et al., 2014; Saylor et al., 2016). We investigated two main questions: 1) What is the relationship between cumulative cART exposure and neuropsychological impairment in PWH? and 2) Based on evidence from existing HIV cohorts, what is the evidence on relationships between cART and memory functions in PWH?
    To address the first question, we evaluated the role of ART exposure as predictor of neurocognitive impairment using univariate analyses and machine learning, while accounting for potential effects of demographic, clinical, and comorbidity-related risk factors in a cohort of 343 PWH. Out of a total of 26 tested variables, two random forest analyses identified the most important characteristics of a neurocognitively impaired group (N=59): Compared to a neurocognitively high performing group (N=132; F1-score=0.79), we uncovered 13 important risk factors; compared to an intermediately performing group (N=152; F1-score=0.75), 16 risk factors emerged. Longer lifetime ART-exposure, especially to integrase inhibitors, was one of the most important predictors of neurocognitive impairment in both analyses (rank 2 of 13 and rank 4 of 16, respectively), superseding effects of age (rank 11/13, rank 15/16) and HIV duration (rank 13/13, rank 16/16). Concerning specific integrase inhibitors, the impaired group had significantly longer dolutegravir exposure (p=.011) compared to the high performing group (p=.012; trend compared to the intermediate group p = 0.063).

    To address the second question, we conducted a systematic review of the current literature on memory functions in cART-treated HIV cohorts. An initial search of four major databases (EMBASE, CINAHL, MEDLINE and PsycINFO) resulted in 4,080 records with 82 potentially relevant full texts. After screening, 31 studies were ultimately included in the review. Of the 31 included studies, 10 were longitudinal and 21 were cross-sectional (two clinical trials and 29 observational studies). Among the longitudinal studies, 7/10 showed improved (verbal) memory in PWH after initiation of cART, with evidence from four comparable studies pointing to effects specifically in patients with impaired memory at baseline. Among the cross-sectional studies, we found equal evidence for reduced (n=7 studies) or similar (n=7 studies) memory performance in PWH compared to the respective control groups. These studies showed no difference in the percentage of PWH receiving ART (χ2[36]=22.49, p=.29). Substantial heterogeneity of the included memory measures, study designs, and cohorts, as well as a lack of specific cART information in the identified cohort studies impeded our ability to draw further conclusions from this literature.
    Understanding the relationship between cART and cognition remains a challenge in HIV research and care, one that is imperative to solve considering the aging demographic in cART-treated PWH today. Apart from retrospective work such as presented in this thesis, more longitudinal studies, ideally randomized controlled trials, as well as experimental work on specific drug-cognition relationships are needed. Information from such studies may further help clinicians optimize treatments strategies for PWH, ultimately leading to increased quality of life for patients.

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.