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Acquired hypogammaglobulinemia in HIV-positive subjects after liver transplantation.

ABSTRACT: As more solid organ transplantations are performed in patients infected with human immunodeficiency virus (HIV), post-transplant complications in this population are becoming better defined.Using serum samples from the Solid Organ Transplantation in HIV: Multi-Site Study, we studied the epidemiology of acquired hypogammaglobulinemia (HGG) after liver transplantation (LT) in 79 HIV-infected individuals with a median CD4 count at enrollment of 288 (interquartile range 200-423) cells/?L. Quantitative immunoglobulin G (IgG) levels before and after LT were measured, with moderate and severe HGG defined as IgG 350-500 mg/dL and <350 mg/dL, respectively. Incidence, risk factors, and associated outcomes of moderate or worse HGG were evaluated using Kaplan-Meier estimator and proportional hazards (PH) models.The 1-year cumulative incidence of moderate or worse HGG was 12% (95% confidence interval [CI]: 6-22%); no new cases were observed between years 1 and 2. In a multivariate PH model, higher pre-transplant model for end-stage liver disease score (P = 0.04) and treated acute rejection (P = 0.04) were both identified as significant predictors of moderate or worse HGG. There was a strong association of IgG levels <500 mg/dL with non-opportunistic serious infection (hazard ratio [95% CI]: 3.5 [1.1-10.6]; P = 0.03) and mortality (3.2 [1.1-9.4]; P = 0.04). These associations held after adjustment for important determinants of infection and survival among the entire cohort.These results suggest that a proportion of HIV-positive LT recipients will develop clinically significant HGG after transplantation.

SUBMITTER: Gregg KS

PROVIDER: S-EPMC3855083 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Acquired hypogammaglobulinemia in HIV-positive subjects after liver transplantation.

Gregg K S KS Barin B B Pitrak D D Ramaprasad C C Pursell K K

Transplant infectious disease : an official journal of the Transplantation Society 20130918 6

<h4>Introduction</h4>As more solid organ transplantations are performed in patients infected with human immunodeficiency virus (HIV), post-transplant complications in this population are becoming better defined.<h4>Methods</h4>Using serum samples from the Solid Organ Transplantation in HIV: Multi-Site Study, we studied the epidemiology of acquired hypogammaglobulinemia (HGG) after liver transplantation (LT) in 79 HIV-infected individuals with a median CD4 count at enrollment of 288 (interquartil ...[more]

PMID: 24103022

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Project description:BackgroundOne of the primary risks of HIV-positive to HIV-positive organ transplantation is loss of virological control because of donor-derived HIV superinfection, which occurs when an HIV-positive individual becomes infected with a new distinct HIV strain. In this study, as part of the larger HIV Organ Policy Equity pilot study, HIV-positive to HIV-positive kidney and liver transplant recipients in the USA were examined for evidence of sustained donor-derived HIV superinfection.MethodsIn this multicentre, prospective, observational study, HIV-positive to HIV-positive kidney and liver transplant recipients were followed in three hospitals in the USA. Candidates with well controlled HIV infection on ART, no active opportunistic infections, and minimum CD4 T-cell counts (>100 cells per μL for liver and >200 cells per μL for kidney per federal guidelines) were eligible to receive a kidney or liver from deceased HIV-positive donors without active infections or neoplasm. Peripheral blood mononuclear cells were collected from donor-recipient pairs at the time of transplantation, and from recipients at several timepoints up to 3 years after transplantation. Donor samples were assessed for HIV RNA viral load, CD4 cell count, and antiretroviral drug-resistant mutations. Donor and recipient HIV proviral DNA, and viral RNA from the viraemic timepoint were sequenced using a site-directed next-generation sequencing assay for the reverse transcriptase and gp41 genes. Neighbour-joining phylogenetic trees and direct sequence comparison were used to detect the presence of HIV superinfection. This study is registered with ClinicalTrials.gov, NCT02602262.Findings14 HIV-positive to HIV-positive kidney and eight liver transplant recipients were followed from March, 2016, to July, 2019. 17 recipients had adequate viral sequences allowing for HIV superinfection assessment. Eight donors were suppressed (viral load <400 copies per mL), and none had multiclass drug-resistant mutations detected. None of the recipients examined had evidence of HIV superinfection. One recipient had a viraemic episode (viral load of 2 080 000 copies per mL) 3 years after transplantation as a result of non-adherence to ART. Only recipient viral sequences were detected during the viraemic episode, suggesting that the donor virus, if present, was not reactivated despite temporary withdrawal of ART.InterpretationThese findings suggest that loss of HIV suppression due to donor-derived HIV superinfection might not be a significant clinical concern in carefully monitored ART suppressed HIV-positive organ recipients.FundingUS National Institute of Allergy and Infectious Diseases and National Cancer Institute.

Project description:BACKGROUND:Depression is a frequent comorbidity in HIV infection that has been associated with worse treatment outcomes and increased mortality. Recent studies suggest that increased innate immune activation and tryptophan catabolism are associated with higher risk of depression in HIV infection and other chronic inflammatory diseases, but the mechanisms leading to depression remain poorly understood. METHODS:The severity of depressive symptoms was assessed by Beck Depression Inventory or Center for Epidemiological Studies Depression Scale. Untargeted metabolomic profiling of plasma from 104 subjects (68 HIV-positive and 36 HIV-negative) across 3 independent cohorts was performed using liquid or gas chromatography followed by mass spectrometry. Cytokine profiling was by Bioplex array. Bioinformatic analysis was performed in Metaboanalyst and R. RESULTS:Decreased monoamine metabolites (phenylacetate, 4-hydroxyphenylacetate) and acylcarnitines (propionylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2-methylbutyrylcarnitine) in plasma distinguished depressed subjects from controls in HIV-positive and HIV-negative cohorts, and these alterations correlated with the severity of depressive symptoms. In HIV-positive subjects, acylcarnitines and other markers of mitochondrial function correlated inversely with tryptophan catabolism, a marker of interferon responses, suggesting interrelationships between inflammatory pathways, tryptophan catabolism, and metabolic alterations associated with depression. Altered metabolites mapped to pathways involved in monoamine metabolism, mitochondrial function, and inflammation, suggesting a model in which complex relationships between monoamine metabolism and mitochondrial bioenergetics contribute to biological mechanisms involved in depression that may be augmented by inflammation during HIV infection. CONCLUSIONS:Integrated approaches targeting inflammation, monoamine metabolism, and mitochondrial pathways may be important for prevention and treatment of depression in people with and without HIV.

Dataset Information

Acquired hypogammaglobulinemia in HIV-positive subjects after liver transplantation.

Publications

Acquired hypogammaglobulinemia in HIV-positive subjects after liver transplantation.

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