Rebound of residual plasma viremia after initial decrease following addition of intravenous immunoglobulin to effective antiretroviral treatment of HIV

<p>Abstract</p> <p>Background</p> <p>High dosage of intravenous immunoglobulin (IVIG) has been observed as a possible activator of HIV gene expression in latently infected resting CD4⁺T-cells, leading to a substantial decrease in both the reservoir and the residual plasma viremia when added to effective ART. IVIG treatment has also been reported to expand T regulatory cells (Tregs). The aim of this study was to evaluate possible long-term effect of IVIG treatment on residual viremia and T-lymphocyte activation.</p> <p>Methods</p> <p>Nine HIV-infected subjects on effective ART included in a previously reported study on IVIG treatment were evaluated 48-104 weeks after therapy. In addition, 14 HIV-infected controls on suppressive ART were included. HIV-1 RNA was analyzed in cell-free plasma by using an ultrasensitive PCR-method with a detection limit of 2 copies/mL. T-lymphocyte activation markers and serum interleukins were measured.</p> <p>Results</p> <p>Plasma residual viremia rebounded to pre-treatment levels, 48-104 weeks after the initial decrease that was observed following treatment with high-dosage IVIG. No long-term effect was observed regarding T-lymphocyte activation markers, T-regulatory cells or serum interleukins. In a post-hoc analysis, a correlation between plasma HIV-1-RNA and CD4⁺T-cell count was found in both IVIG-treated patients and controls.</p> <p>Conclusions</p> <p>These results indicate that the decrease in the latent HIV-1 pool observed during IVIG treatment is transient. Although not our primary objective, we found a correlation between HIV-1 RNA and CD4⁺T-cell count suggesting the possibility that patients with a higher CD4⁺T-cell count might harbor a larger residual pool of latently infected CD4⁺T-cells.</p

Case report of eosinophilic granulomatosis with polyangitis presenting as acute myocarditis

: This case presents a challenging diagnosis of EGPA presenting as eosinophilic myocarditis. It is a condition that can mimic many other diseases and where prompt diagnosis and early treatment is essential for recovery. The diagnosis was made after an endomyocardial biopsy (EMB) and showed the importance of EMB in the diagnostic work-up

Postprandial levels of GLP-1, GIP, and glucagon after two years of weight loss with a Paleolithic diet : a randomized controlled trial in healthy obese women

OBJECTIVE: To investigate how weight loss by different diets impacts on postprandial levels of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon. METHODS: In this single-centre, parallel group 2-year trial, 70 healthy postmenopausal obese women were randomized to the Paleolithic diet or a healthy control diet based on Nordic Nutrition Recommendations. Both diets were without calorie restriction. The primary outcome was the change in fat mass. Here, secondary analyses on GLP-1, GIP, and glucagon measured during an OGTT are described. RESULTS: In the Paleolithic diet group, mean weight loss compared to baseline was 11% at 6 months, and 10% at 24 months. In the control diet group, mean weight loss was 6% after 6 and 24 months (P = 0.0001 and P = 0.049 for the comparison between groups at 6 and 24 months respectively). Compared to baseline, the mean incremental area under the curve (iAUC) for GLP-1 increased by 34% and 45% after 6 and 24 months in the Paleolithic diet group, and increased by 59% after 24 months in the control diet group. The mean iAUC for GIP increased only in the Paleolithic diet group. The AUC for glucagon increased during the first 6 months in both groups. The fasting glucagon increase correlated with the β-hydroxybutyrate increase. CONCLUSIONS: Weight loss caused an increase in postprandial GLP-1 levels and a further rise occurred during weight maintenance. Postprandial GIP levels increased only after the Paleolithic diet. Reduced postprandial glucagon suppression may be caused by a catabolic state

Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients

Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method.With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use

CSF NFL levels before-after combination antiretroviral treatment (cART) initiation.

<p>Overall CSF NFL levels decreased in 63% of the patients after initiation of cART (p<0.01), demonstrated as a lower CSF NFL geometric mean (dotted line) after initiation of cART. 33% of the patents had elevated levels of CSF NFL at baseline and 81% of those exhibited reduction in their CSF NFL levels after treatment (p<0.01). 35% of patients with pathological CSF NFL at baseline normalized their levels (green colored). Those with normal CSF NFL at baseline exhibited no significant reduction in CSF NFL (blue colored). Three patients with normal baseline CSF NFL exhibited elevated levels of CSF NFL after cART initiation (red colored).</p

Cross-sectional analysis of CSF NFL in HIV disease.

<p>Included were 14 subjects diagnosed with HIV-associated dementia (HAD); HIV positive neuroasymptomatic subjects (NA) without antiretroviral treatment stratified according to levels of blood CD4 T-cells <50 (n = 42), 50–199 (n = 49), 200–349 (n = 52) and >350 (n = 57); 85 subjects on combination antiretroviral treatment (ART) for at least one year and plasma HIV-RNA <50 copies/ml and 204 HIV seronegative volunteers (HIV-neg). CSF NFL concentrations were higher in patients with HAD compared to all other groups. Elevated levels of CSF NFL was also found in subjects with a CD4+ T-cell count below 50 cells/mL compared to groups in higher CD4+ T-cell count strata. Whiskers represent full range</p

CSF NFL related to age and treatment effect.

<p>Since CSF NFL increases with age, we analyzed the group differences with a linear mixed effects model with age as covariate. This implies a model with three parallel regression lines where the group differences correspond to the vertical distances between the regression lines. The group differences can be expressed as the corresponding age increase needed for an equivalent difference. The 95% prediction interval of CSF NFL levels of HIV-negative controls is demonstrated as dotted lines (Neg 95% PI). Concentrations of CSF NFL in neuroasymptomatic untreated HIV-infected subjects (No ART) were equivalent to those of HIV-negative subjects (negative) who were 18.5 years older (p<0.001). CSF NFL concentrations in the treated group (ART) were equivalent to those of HIV-negative subjects who were 3.9 years older (p<0.01).</p

Univariate correlation (left columns) and multiple linear regression (right columns) determining predictors of log₁₀ CSF NFL in HIV-infected neuroasymptomatic patients with and without antiretroviral treatment.

<p>*CD4+ T-cell count was inverse transformed (1/(CD4+45·3) NS = Not significant.</p

Correlations with CD4 T-cell counts and CSF NFL.

<p>A loess regression (dotted line) suggested an inverse transformation of CD4+ T-cell counts. Visual inspection reveals a rapid decline with increasing CD4+ T-cell counts that flattens out at around 250 cells/mL. The relationship between log₁₀ CSF NFL levels and CD4+ cell counts were fitted with non-linear regression using the function Log CSF NFL  =  b1 + b2/(CD4 + b3) (filled line). CSF NFL concentrations in patients with HIV-associated dementia (HAD) diagnosis, marked with red color in the figure were significantly elevated also compared to untreated neuroasymptomatic patients with equivalently low CD4+ T-cell counts, p<0.001.</p