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

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

Author information

1
aUniversity of Hawaii at Manoa, Honolulu, Hawaii bUniversity of California, San Francisco, California, USA cFaculty of Medicine, Chulalongkorn University dPhramongkutklao Hospital eSEARCH, The Thai Red Cross AIDS Research Center fHIV-NAT, The Thai Red Cross AIDS Research Center, Bangkok, Thailand. *Kalpana J. Kallianpur and Victor G. Valcour contributed equally to the writing of the manuscript.

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.

PMID:
25232899
PMCID:
PMC4170526
DOI:
10.1097/QAD.0000000000000306
[Indexed for MEDLINE]
Free PMC Article

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