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

Autor: Kallianpur, KJ, Valcour, VG, Lerdlum, S, Busovaca, E, Agsalda, M, Sithinamsuwan, P, Chalermchai, T, Fletcher, JLK, Tipsuk, S, Shikuma, CM, Shiramizu, BT, Ananworanich, J
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Kallianpur, KJ; Valcour, VG; Lerdlum, S; Busovaca, E; Agsalda, M; Sithinamsuwan, P; et al.(2014). HIV DNA in CD14+reservoirs is associated with regional brain atrophy in patients naive to combination antiretroviral therapy. AIDS, 28(11), 1619-1624. doi: 10.1097/QAD.0000000000000306. UCSF: Retrieved from: http://www.escholarship.org/uc/item/8pm7q162
Popis: 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.
Databáze: OpenAIRE