Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course.
OBJECTIVE
To characterize HIV-1 env compartmentalization between cerebrospinal fluid (CSF) and peripheral blood plasma over all stages of the HIV-1 disease course, and to determine the relationship between the extent of CSF HIV-1 env compartmentalization and clinical neurologic disease status.


METHODS
Paired blood plasma and CSF specimens were collected from 66 HIV-infected patients cross-sectionally representing all major clinical stages relating to HIV-associated neurologic disease, including primary infection, asymptomatic chronic infection, chronic infection with minor global impairment, and immune deficiency with HIV-associated dementia.


METHODS
Heteroduplex tracking assays and bulk sequence analysis targeting the V1/V2, C2-V3, and V4/V5 regions of env were performed to characterize the genetic makeup of complex HIV-1 populations in the cross-sectional blood plasma and CSF specimens. The levels of blood plasma/CSF env compartmentalization were quantified and compared across the different clinical stages of HIV-1 neurologic disease.


RESULTS
Blood plasma/CSF env compartmentalization levels varied considerably by disease stage and were generally consistent across all three regions of env characterized. Little or no compartmentalization was observed in non-impaired individuals with primary HIV-1 infection. Compartmentalization levels were elevated in chronically infected patients, but were not significantly different between mildly impaired and non-impaired patients. Patients with HIV-associated dementia showed significantly greater blood plasma/CSF env compartmentalization relative to other groups.


CONCLUSIONS
: Increased CSF compartmentalization of the HIV-1 env gene, which may reflect independent HIV-1 replication and evolution within the central nervous system, is specifically associated with HIV-associated dementia and not the less severe forms of HIV-1 neurologic disease.
Harrington
Patrick R
PR
Lineberger Comprehensive Cancer Center and UNC Center for AIDS Research, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599-7295, USA.
Schnell
Gretja
G
Letendre
Scott L
SL
Ritola
Kimberly
K
Robertson
Kevin
K
Hall
Colin
C
Burch
Christina L
CL
Jabara
Cassandra B
CB
Moore
Dominic T
DT
Ellis
Ronald J
RJ
Price
Richard W
RW
Swanstrom
Ronald
R
D015526:AIDS Dementia Complex / Q000150:complications / Q000378:metabolism; D002140:California; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D018450:Disease Progression; D015752:Genes, env; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000150:complications; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid* / Q000150:complications; D009657:North Carolina; D012495:San Francisco