HIV DNA in CD14+ reservoirs is associated with regional brain atrophy in patients naive to combination antiretroviral therapy
| Autor: | Kallianpur, Kalpana J, Valcour, Victor G, Lerdlum, Sukalaya, Busovaca, Edgar, Agsalda, Melissa, Sithinamsuwan, Pasiri, Chalermchai, Thep, Fletcher, James LK, Tipsuk, Somporn, Shikuma, Cecilia M, Shiramizu, Bruce T, Ananworanich, Jintanat, SEARCH 011 study group |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Asian Continental Ancestry Group Male reservoir nucleus accumbens Lipopolysaccharide Receptors HIV Infections Real-Time Polymerase Chain Reaction Medical and Health Sciences Monocytes brainstem Asian People HIV DNA Clinical Research Virology Humans Viral Prospective Studies Antigens SEARCH 011 study group HIV-associated neurocognitive impairment Psychology and Cognitive Sciences Neurosciences Evaluation of treatments and therapeutic interventions Brain DNA gray matter Viral Load Biological Sciences Thailand Brain Disorders Infectious Diseases 6.1 Pharmaceuticals HIV/AIDS Female Atrophy Infection CD14 |
| Zdroj: | AIDS (London, England), vol 28, iss 11 |
| Popis: | ObjectiveTo examine associations between regional brain volumes and HIV DNA in peripheral CD14 cells (monocytes) among HIV-infected individuals naive to combination antiretroviral therapy (cART).DesignA 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.MethodsCD14 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).ResultsWe 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.ConclusionHIV 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. |
| Databáze: | OpenAIRE |
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