title: Circulating HIV DNA Correlates With Neurocognitive Impairment in Older HIV-infected Adults on Suppressive ART.
abstract: Older HIV-infected adults have a higher risk of neurocognitive impairment, but the underlying mechanisms are poorly understood. Here, we investigated the associations between levels of HIV DNA in peripheral blood, soluble markers of inflammation and cellular trafficking in blood and cerebrospinal fluid (CSF) and neurocognitive functioning among 18 younger (22-40 years) and 26 older (50-71 years) HIV-infected subjects, who were administered a comprehensive neurocognitive battery. Older HIV-infected individuals presented higher levels of inflammation in CSF and blood compared to younger individuals, but no difference was observed in HIV DNA levels. Among older participants, higher HIV DNA levels were significantly associated with more severe neurocognitive impairment (p = 0.005), particularly in the Executive Functions domain (p = 0.004). No association was observed between HIV DNA and neurocognition among younger individuals. Despite significantly increased inflammation observed in the older group, none of the inflammatory markers were associated with neurocognitive impairment among older HIV+ individuals (p > 0.05). Our study supports the involvement of peripheral HIV DNA reservoir in the pathogenesis of neurocognitive disorder during suppressive ART. Correlates of neurocognitive impairment might differ between younger and older adults, suggesting that future treatment and prevention strategies for HIV-associated neurocognitive disorders likely need to be tailored based on age.
authors.affiliation: University of California San Diego, La Jolla, CA, USA.
authors.forename: Michelli Faria
authors.initials: MF
authors.lastname: de Oliveira
authors.forename: Ben
authors.initials: B
authors.lastname: Murrell
authors.affiliation: University of California San Diego, La Jolla, CA, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Murrel
authors.affiliation: University of California San Diego, La Jolla, CA, USA.
authors.forename: Josué
authors.initials: J
authors.lastname: Pérez-Santiago
authors.affiliation: University of California San Diego, La Jolla, CA, USA.
authors.forename: Milenka
authors.initials: M
authors.lastname: Vargas
authors.affiliation: HIV Neurobehavioral Research Center, San Diego, CA, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: HIV Neurobehavioral Research Center, San Diego, CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.affiliation: HIV Neurobehavioral Research Center, San Diego, CA, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: University of Houston, Houston, TX, USA.
authors.forename: Steven Paul
authors.initials: SP
authors.lastname: Woods
authors.affiliation: University of California San Diego, La Jolla, CA, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Gianella
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000473:pathology*; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid; D056344:Executive Function / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood* / Q000134:cerebrospinal fluid; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D012367:RNA, Viral