Advanced liver fibrosis by transient elastography, Fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: Role of vitamin D levels

Background and Aim: Vitamin D insufficiency plays an important role in liver fibrosis in hepatitis C virus (HCV)-infected patients. We assessed liver fibrosis by transient elastography and 25 hydroxy vitamin D [25(OH)D] status in HCV-infected patients, with (HIV/HCV) or without HIV co-infection (HCV) from Thailand. Methods: Fibrosis stage was defined as mild ( 14 kPa). Hypovitaminosis D was defined as 25(OH)D 1.45 (6.30, 2.70-14.74), P 1.45, and hypovitaminosis D are strong and independent predictors for the presence of advanced fibrosis in our HCV-infected patients. These data highlight the urgent need of HCV treatment and vitamin D supplement in resource-limited setting

HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients.

OBJECTIVES: Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury. METHODS: We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+) enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF). RESULTS: The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions. INTERPRETATION: Reservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS

HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients.

ObjectivesCognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury.MethodsWe enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+) enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).ResultsThe mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.InterpretationReservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS

HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients.

ObjectivesCognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury.MethodsWe enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+) enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).ResultsThe mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.InterpretationReservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS

Plasma CD14⁺ HIV DNA and plasma neopterin (left, <i>p</i> = 0.0473, adjusted <i>r</i>² = 0.0662) and CSF neopterin (right, <i>p = </i>0.023, adjusted <i>r</i>² = 0.123) by univariate regression.

<p>Plasma CD14⁺ HIV DNA and plasma neopterin (left, <i>p</i> = 0.0473, adjusted <i>r</i>² = 0.0662) and CSF neopterin (right, <i>p = </i>0.023, adjusted <i>r</i>² = 0.123) by univariate regression.</p

MRS voxel locations (representative examples).

<p>1. Occipital grey matter, 2. Frontal grey matter, 3. Frontal white matter, 4. Basal ganglia.</p

Receiver operating characteristic (ROC) curve for level CD14⁺ HIV DNA identifying HAND.

<p>ROC of CD14⁺ HIV DNA only = 0.7922, ROC adjusting for CD4⁺ T-lymphocyte and plasma HIV RNA: 0.8247.</p

Clinical characteristic of enrollees. For CSF, <i>n</i> = 22 for NL and 21 for HAND groups.

<p>Clinical characteristic of enrollees. For CSF, <i>n</i> = 22 for NL and 21 for HAND groups.</p