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

AIDS. 2014 Jul 17;28(11):1619-24. doi: 10.1097/QAD.0000000000000306.

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 log10 plasma HIV RNA of 4.8 (0.73). Median (interquartile range, IQR) HIV DNA copy number per 10 CD14 cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/10 cells 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/10 cells 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Asian Continental Ancestry Group
  • Atrophy*
  • Brain / pathology*
  • DNA, Viral / analysis*
  • DNA, Viral / genetics
  • Female
  • HIV Infections / complications
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV Infections / virology*
  • Humans
  • Lipopolysaccharide Receptors / analysis*
  • Male
  • Monocytes / chemistry
  • Monocytes / immunology
  • Monocytes / virology*
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Thailand
  • Viral Load

Substances

  • DNA, Viral
  • Lipopolysaccharide Receptors