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Recent advances in experimental models, methodology, and our understanding of disease processes at the molecular and cellular levels reveal opioid-HIV interactions with increasing clarity. However, despite the substantial new insight, the unique impact of opioids on the severity, progression, and prognosis of neuroHIV and HIV-associated neurocognitive disorders (HAND) are not fully understood. In this review, we explore, in detail, what is currently known about mechanisms underlying opioid interactions with HIV, with emphasis on individual HIV-1-expressed gene products at the molecular, cellular and systems levels. Furthermore, we review preclinical and clinical studies with a focus on key considerations when addressing questions of whether opioid-HIV interactive pathogenesis results in unique structural or functional deficits not seen with either disease alone. These considerations include, understanding the combined consequences of HIV-1 genetic variants, host variants, and \u03bc-opioid receptor (MOR) and HIV chemokine co-receptor interactions on the comorbidity. Lastly, we present topics that need to be considered in the future to better understand the unique contributions of opioids to the pathophysiology of neuroHIV.<\/jats:p>","DOI":"10.1007\/s11481-020-09941-8","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T08:04:43Z","timestamp":1599033883000},"page":"584-627","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Opioid and neuroHIV Comorbidity \u2013 Current and Future Perspectives"],"prefix":"10.1007","volume":"15","author":[{"given":"Sylvia","family":"Fitting","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MaryPeace","family":"McRae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-0332","authenticated-orcid":false,"given":"Kurt F.","family":"Hauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,2]]},"reference":[{"key":"9941_CR1","doi-asserted-by":"crossref","first-page":"107670","DOI":"10.1016\/j.drugalcdep.2019.107670","volume":"206","author":"JW Adams","year":"2020","unstructured":"Adams JW, Marshall BDL, Mohd Salleh NA, Barrios R, Nolan S, Milloy MJ (2020) Receipt of opioid agonist treatment halves the risk of HIV-1 RNA viral load rebound through improved ART adherence for HIV-infected women who use illicit drugs. 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