Dual-mixed HIV-1 coreceptor tropism and HIV-associated neurocognitive deficits.
HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell counts and accelerated disease progression, but the role of X4 tropism in HIV-associated neurocognitive disorders (HAND) has not previously been described. This longitudinal study evaluated data on 197 visits from 72 recently HIV-infected persons who had undergone up to four sequential neurocognitive assessments over a median of 160 days (IQR, 138–192). Phenotypic tropism testing (Trofile ES, Monogram, Biosciences) was performed on stored blood samples. Multivariable mixed model repeated measures regression was used to determine the association between HAND and dual-mixed (DM) viral tropism, estimated duration of infection (EDI), HIV RNA, CD4 count, and problematic methamphetamine use. Six subjects (8.3 %) had DM at their first neurocognitive assessment and four converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of 10.1 months (IQR, 7.2–12.2). There were 44 (61.1 %) subjects who demonstrated HAND on at least one study visit. HAND was associated with DM tropism (odds ratio, 4.4; 95 % CI, 0.9–20.5) and shorter EDI (odds ratio 1.1 per month earlier; 95 % CI, 1.0–1.2). This study found that recency of HIV-1 infection and the development of DM tropism may be associated with HAND in the relatively early stage of infection. Together, these data suggest that viral interaction with cellular receptors may play an important role in the early manifestation of HAND.
Sheldon R
SR
Morris
Steven Paul
SP
Woods
Reena
R
Deutsch
Susan J
SJ
Little
Gabriel
G
Wagner
Erin E
EE
Morgan
Robert K
RK
Heaton
Scott L
SL
Letendre
Igor
I
Grant
Davey M
DM
Smith
D000328:Adult; D018791:CD4 Lymphocyte Count; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology / Q000821:virology; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000523:psychology; D056189:Viral Tropism
C584933:CCR5 protein, human; C527276:CXCR4 protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4