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Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting \u201cBiotypes of CNS Complications in People Living with HIV,\u201d held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.<\/jats:p>","DOI":"10.1093\/infdis\/jiac387","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T16:49:05Z","timestamp":1679071745000},"page":"S16-S29","source":"Crossref","is-referenced-by-count":29,"title":["Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus"],"prefix":"10.1093","volume":"227","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9483-1117","authenticated-orcid":false,"given":"Erin E","family":"O\u2019Connor","sequence":"first","affiliation":[{"name":"Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine , Baltimore, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith V","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine , Stanford, California , USA"},{"name":"Center for Health Sciences, SRI International , Menlo Park, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine , Baltimore, Maryland , USA"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dima A","family":"Hammoud","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Imaging, Radiology and Imaging Sciences, NIH Clinical Center , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony W","family":"Wilson","sequence":"additional","affiliation":[{"name":"Institute for Human Neuroscience, Boys Town National Research Hospital , Boys Town, Nebraska , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann B","family":"Ragin","sequence":"additional","affiliation":[{"name":"Department of Radiology, Feinberg School of Medicine, Northwestern University , Chicago, Illinois , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina S","family":"Meade","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Coughlin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine , St Louis, Missouri , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau M","family":"Ances","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"2023031716485745900_","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/infdis\/jis326","article-title":"Central nervous system viral invasion and inflammation during acute HIV infection","volume":"206","author":"Valcour","year":"2012","journal-title":"J Infect Dis"},{"key":"2023031716485745900_","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1042\/CS20050278","article-title":"Viruses and the brain: from inflammation to dementia","volume":"110","author":"Wang","year":"2006","journal-title":"Clin Sci"},{"key":"2023031716485745900_","first-page":"589","article-title":"Novel machine learning identifies brain patterns distinguishing 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