title: Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria.
abstract: Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample. Utilizing demographically adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS of ≥0.5 indicating cognitive impairment. In a linear regression adjusting for plasma HIV RNA, CD4 and lymphocyte count, Beck's depression score, and years of education, there was 0.04 lower log10HIV DNA copies within T&B lymphocytes per unit increase in global T score (p = 0.02). Adjusting for the same variables in a logistic regression, the odds of cognitive impairment were 6.2 times greater per log10increase in HIV DNA within T&B lymphocytes (p = 0.048). The association between cognitive impairment and HIV DNA within CD14+ monocytes did not reach statistical significance. In this pretreatment cohort with mild cognitive dysfunction, we found a strong association between levels of HIV DNA within the lymphocyte subset and HAND independent of plasma HIV RNA. These findings likely reflect the neurologic impact of a larger HIV reservoir and active viral replication.
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: Jibreel
authors.initials: J
authors.lastname: Jumare
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Sunshine
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Hayat
authors.initials: H
authors.lastname: Ahmed
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: Samer S
authors.initials: SS
authors.lastname: El-Kamary
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Magder
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Hungerford
authors.affiliation: Temple University School of Medicine, Philadelphia, PA, 19140, USA.
authors.forename: Tricia
authors.initials: T
authors.lastname: Burdo
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Eyzaguirre
authors.affiliation: School of Medicine, University of California San Diego, San Diego, CA, 92103, USA.
authors.forename: Anya
authors.initials: A
authors.lastname: Umlauf
authors.affiliation: School of Medicine, University of California San Diego, San Diego, CA, 92103, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Cherner
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: Alash'le
authors.initials: A
authors.lastname: Abimiku
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: Man
authors.initials: M
authors.lastname: Charurat
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Li
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD, 21201, USA. wroyal@som.umaryland.edu.
authors.forename: Walter
authors.initials: W
authors.lastname: Royal
mesh_terms: D015526:AIDS Dementia Complex / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000821:virology*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000821:virology*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D009549:Nigeria; D012367:RNA, Viral / Q000097:blood*; D019713:Receptors, CCR5 / Q000097:blood
chemical_list: D015415:Biomarkers; C584933:CCR5 protein, human; D004279:DNA, Viral; D012367:RNA, Viral; D019713:Receptors, CCR5
keywords: HIV DNA; Mononuclear cells; Neurocognitive disorders; Nigeria