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

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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 106 CD14+ cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/106 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/106 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.

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