Circulating proviral HIV DNA and HIV-associated dementia.
OBJECTIVE
Individuals continue to develop HIV-1-associated dementia (HAD) despite treatment with highly active antiretroviral therapy (HAART). Monocytes/macrophages (M/MPhi) can harbor proviral DNA that is not eradicated by HAART. To determine if HAD is associated with the level of HIV-1 infection within circulating leukocytes, we quantified HIV-1 DNA copy number in peripheral blood mononuclear cells (PBMC), and in PBMC subsets.


METHODS
Cross-sectional analysis within the Hawaii Aging with HIV Cohort comparing participants with HAD to those with normal cognition (NC).


METHODS
Real-time PCR assays assessing HIV DNA copy number/1 x 10 cells were performed on PBMC and subsets.


RESULTS
Individuals with HAD (n = 27) had a median (interquartile range) of 9.11 (37.20) HIV DNA per 1 x 10 PBMC compared to 0.49 (0.89) HIV DNA per 1 x 10 PBMC in individuals with NC (n = 22). Using a univariate analysis in the subset of individuals with undetectable viral load (HAD, n = 11; NC, n = 13), the odds of HAD attributable to HIV DNA copy number was 2.76 (1.28-5.94), P < 0.01. Preliminary analysis of a small subset of patients (n = 5) suggested that the primary source of HIV DNA may be the activated M/MPhi (CD14/CD16) subset.


CONCLUSIONS
These findings suggest a potentially important association between circulating provirus and HAD.
Shiramizu
Bruce
B
Hawaii AIDS Clinical Research Program, University of Hawaii, Honolulu, Hawaii, USA. bshirami@hawaii.edu
Gartner
Suzanne
S
Williams
Andrew
A
Shikuma
Cecilia
C
Ratto-Kim
Silvia
S
Watters
Michael
M
Aguon
Joleen
J
Valcour
Victor
V
D015526:AIDS Dementia Complex / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011533:Proviruses; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D019562:Viral Load / Q000379:methods
D015703:Antigens, CD; D004279:DNA, Viral