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. 2005 Jan 3;19(1):45-52.
doi: 10.1097/00002030-200501030-00005.

Circulating proviral HIV DNA and HIV-associated dementia

Bruce Shiramizu  1 , Suzanne Gartner, Andrew Williams, Cecilia Shikuma, Silvia Ratto-Kim, Michael Watters, Joleen Aguon, Victor Valcour
Affiliations

Circulating proviral HIV DNA and HIV-associated dementia

Bruce Shiramizu et al. AIDS. .

Abstract

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.

Design: 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.

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Figures

Fig. 1
Fig. 1. Box plots of HIV DNA
(a) HIV DNA of all individuals (n = 49) with NC and HAD. (b) Similar plot of HIV DNA of individuals with undetectable plasma viral levels (n = 24). Both plots demonstrate the skewed distribution of HIV DNA while showing the significant difference between the medians when comparing individuals with NC to those with HAD.
Fig. 2
Fig. 2. Representative immunofluorescence analysis of CD14/CD16 subset
Dot plot of the purified monocytes (a), which were analyzed prior to CD16 isolation (b). PE, Phycoerythrin; FITC, fluorescein isothiocyanate.
Fig. 3
Fig. 3. Representative real-time PCR standard curves with unknown examples
Unknown samples were assayed using β-globin (a) and HIV-1 (b) primers. Samples falling within the standard curve (a) and samples less than the lower limits of the standard curve (b) were analyzed with the iCycler IQ Software Program (BioRad). Samples falling below the lower limits of the standard curve are extrapolated for HIV DNA copy number per million assuming a linear relationship.
See this image and copyright information in PMC

References

    1. Gartner S. HIV infection and dementia. Science. 2000;287:602–604. - PubMed
    1. Major Eo, Rausch D, Marra C, Clifford D. HIV-associated dementia. Science. 2000;288:440–442. - PubMed
    1. Ryan LA, Cotter RL, Zink WE, 2nd, Gendelman HE, Zheng J. Macrophages, chemokines and neuronal injury in HIV-1-associated dementia. Cell Mol Biol (Noisy-le-Grand) 2002;48 :137–150. - PubMed
    1. Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, et al. HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol. 2002;8:136–142. - PubMed
    1. McArthur JC, Haughey N, Gartner S, Conant K, Pardo C, Nath A, et al. Human immunodeficiency virus-associated dementia: an evolving disease. J Neurovirol. 2003;9:205–221. - PubMed

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