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HIV DNA in CD14+reservoirs is associated with regional brain atrophy in patients naive to combination antiretroviral therapy

  • Author(s): Kallianpur, KJ
  • Valcour, VG
  • Lerdlum, S
  • Busovaca, E
  • Agsalda, M
  • Sithinamsuwan, P
  • Chalermchai, T
  • Fletcher, JLK
  • Tipsuk, S
  • Shikuma, CM
  • Shiramizu, BT
  • Ananworanich, J
  • et al.

Published Web Location

http://www.ncbi.nlm.nih.gov/pubmed/25232899
No data is associated with this publication.
Abstract

Objective: To examine associations between regional brain volumes and HIV DNA in peripheral CD14+cells (monocytes) among HIV-infected individuals naive to combination antiretroviral therapy (cART). Design: A prospective study of HIV-infected Thai individuals who met Thai national criteria for cART initiation. Enrolment was stratified by HIV DNA in a blinded fashion. Methods: CD14+cells were isolated from peripheral mononuclear cells to high purity (median 91.4% monocytes by flow cytometry), and HIV DNA was quantified by multiplex real-time PCR. Baseline regional brain volumes obtained by T1-weighted 1.5-Tesla MRI were compared between HIV DNA groups using analysis of covariance (ANCOVA). Results: We studied 60 individuals with mean (SD) age of 34.7 (7.0) years, CD4+T-lymphocyte count of 232 (137) cells/μl and log10plasma HIV RNA of 4.8 (0.73). Median (interquartile range, IQR) HIV DNA copy number per 106CD14+cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/106cells for this cohort, a threshold value above which CD14+HIV DNA identified HIV-associated neurocognitive disorders (HANDs), we found that CD14+HIV DNA≥45 copies/106cells was associated with reduced volumes of the nucleus accumbens (P=0.021), brainstem (P=0.033) and total gray matter (P=0.045) independently of age, CD4+cell count and intracranial volume. Conclusion: HIV DNA burden in CD14+monocytes is directly linked to brain volumetric loss. Our findings implicate peripheral viral reservoirs in HIV-associated brain atrophy and support their involvement in the neuropathogenesis of HAND, underscoring the need for therapies that target these cells. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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