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

Kallianpur, Kalpana J.a,*; Valcour, Victor G.b,*; Lerdlum, Sukalayac; Busovaca, Edgarb; Agsalda, Melissaa; Sithinamsuwan, Pasirid; Chalermchai, Thepe; Fletcher, James L.K.e; Tipsuk, Somporne; Shikuma, Cecilia M.a; Shiramizu, Bruce T.a; Ananworanich, Jintanatc,e,f

AIDS:
doi: 10.1097/QAD.0000000000000306
Clinical Science
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.

Author Information

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.

Correspondence to Kalpana J. Kallianpur, Hawaii Center for AIDS, John A. Burns School of Medicine, 651 Ilalo Street, BSB 231-C, Honolulu, HI 96813, USA. E-mail: kalpana@hawaii.edu.

Received 21 January, 2014

Revised 9 April, 2014

Accepted 10 April, 2014

© 2014 Lippincott Williams & Wilkins, Inc.