Joerg Roeling

Ludwig-Maximilians-University of Munich, München, Bavaria, Germany

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Publications (6)19.04 Total impact

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    ABSTRACT: Excessive immune activation is a hallmark of chronic uncontrolled HIV infection. During the past years, growing evidence suggests that immune inhibitory signals also play an important role in progressive disease. However, the relationship between positive and negative immune signals on HIV-specific CD8 T cells has not been studied in detail so far in chronic HIV-1 infection. In this study, the expression of markers of positive (CD38) and negative (PD-1) immune signals on virus-specific CD8 T cells in chronic, untreated HIV-1 infection was evaluated using intracellular cytokine staining. Viral escape mutations were assessed by autologous virus sequence analysis and subsequent peptide titration assays. Single-epitope CD8 T-cell responses toward Gag, Pol, and Nef were compared in 12 HIV-1 controllers (viral load <5,000 cp/ml) and 12 HIV-1 progressors (viral load >50,000 cp/ml) and a highly significant increase of CD38/PD-1 co-expression on virus-specific CD8 T cells in progressors was found (P < 0.0001). The level of CD38/PD-1 co-expression was independent of epitope specificity. Longitudinal follow-up revealed a clear drop in CD38/PD-1 co-expression on virus-specific CD8 T cells after the suppression of antigen following either viral escape mutation or the initiation of HAART (P = 0.004). Antigen persistence with a fluctuating viral load revealed stable levels of CD38/PD-1 co-expression whereas significant rises in viral load were accompanied or even preceded by substantial increases in CD38/PD-1 co-expression. The CD38/PD-1 phenotype clearly distinguishes HIV-specific CD8 T-cell responses between controllers and progressors. Whether it plays a causative role in disease progression remains debatable. J. Med. Virol. 82:358-370, 2010. (c) 2010 Wiley-Liss, Inc.
    No preview · Article · Mar 2010 · Journal of Medical Virology
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    ABSTRACT: Renal disease is becoming an increasingly prevalent entity in human immunodeficiency virus (HIV)-infected patients; it occurs in a variety of clinical settings and is associated with histopathological changes. HIV-related renal impairment can present as acute or chronic kidney disease; it can be caused directly or indirectly by HIV and/or by drug-related effects that are directly nephrotoxic or lead to changes in renal function by inducing metabolic vaculopathy and renal damage. Acute renal failure is frequently caused by the toxic effects of antiretroviral therapy or nephrotoxic antimicrobial substances used in the treatment of opportunistic infections. Chronic renal disease can be caused by multiple pathophysiological mechanisms, leading to HIV-associated nephropathy, a form of collapsing focal glomerulosclerosis, thrombotic microangiopathy, and various forms of immune complex glomerulonephritis. The increase in life expectancy and alteration of lipid metabolism due to receipt of highly active antiretroviral therapy are expected to result in an increased prevalence of diabetes and hypertension and, thus, to secondary diabetic and hypertensive renal damage. Antiretroviral agents, such as indinavir and tenofovir, have been associated with nephrotoxic drug effects that have been shown to be reversible in most cases. In this article, we review the current knowledge about acute and chronic HIV-associated renal disease, metabolic alterations and related nephropathies, and toxic drug effects of combination antiretroviral pharmacotherapy.
    Preview · Article · Jun 2006 · Clinical Infectious Diseases
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    ABSTRACT: To evaluate the prevalence and origin of macroenzyme creatine kinase type 2 (Macro CK2) in HIV-1-infected patients on antiretroviral treatment. CK, CK-MB activity and protein weight, electrophoretic behaviour, glomerular filtration rate (GFR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), bone alkaline phosphatase (AP), beta2-microglobulin serum levels and proteinuria were analysed in 468 HIV-infected outpatients. Sera with detectable Macro CK2 were further analysed using immunoblotting. CK-MB isoenzyme activity and mass concentration revealed the presence of Macro CK2 in 32/408 (7.8%) outpatients. Tenofovir DF (TDF) treatment was a prominent common feature in these patients. Prospective examination of sera from 41 patients collected prior to and during TDF exposure showed Macro CK2 in 20/41 (48%) TDF-treated patients and in 0/19 control sera from patients with TDF-free regimens. Macro CK2 was not present prior to TDF exposure. Patients with Macro CK2 showed a significant elevation of serum beta2-microglobulin levels. GFR, AST/ALT ratio, bone AP and proteinuria remained unchanged. Electrophoresis and immunoblotting demonstrated that the Macro CK2 in TDF-treated patients consisted of the ubiquitous (uMtCK) and not the sarcomeric type (sMtCK) of mitochondrial CK (MtCK). Macro CK2 consisting of uMtCK is associated with the use of TDF-containing regimens. Whether the appearance of uMtCK in these patients reflects mitochondrial damage remains to be clarified.
    Full-text · Article · Feb 2006 · Antiviral therapy
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    ABSTRACT: Therapeutic drug monitoring (TDM) is gaining importance for improving the success of antiretroviral treatment in human immunodeficiency virus-infected patients. However, enfuvirtide (ENF) concentrations are not regularly determined. The objective of this work was to study the pharmacokinetics (PK) of ENF in patients treated in routine clinical settings, to develop a population PK model describing the concentration-time profile, and to establish PK reference values. A liquid chromatography-tandem mass spectrometry method was developed and applied to serum samples submitted for TDM. A two-compartment model with linear absorption and elimination was fitted to 329 concentrations from 131 patients. The PK model was used for simulations resulting in percentile curves for ENF levels for the full dosing interval. The model predicted that a median concentration of 1,968 ng/ml would be reached 12 h after administration of 90 mg of ENF, and 23% and 58% of patients are expected to have concentrations below 1,000 ng/ml and 2,200 ng/ml, respectively. Both values have been proposed as cutoffs for virological efficacy. The median maximum concentration of drug in serum (Cmax) of 3,943 ng/ml, predicted for 3 h after drug administration, is lower than the Cmax reported previously. We found an enormous interpatient variability at every time point, with concentration spectrums covering >1 log and 52% and 123% interindividual variabilities in the typical clearance and volume of distribution, respectively, in contrast to preexisting PK data. In summary, ENF levels are lower and more variable than expected. Many patients may achieve insufficient concentrations. Further covariate analysis in the population PK model might help to identify factors influencing the variability in ENF concentrations.
    Full-text · Article · Feb 2006 · Antimicrobial Agents and Chemotherapy
  • J. Röling · F.-D. Goebel

    No preview · Article · Oct 2005 · Notfall & Hausarztmedizin
  • J Röling · R Draenert · F D Goebel
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    ABSTRACT: Highly active antiretroviral therapy (HAART) has markedly decreased HIV-associated mortality. It consists of a combination of three antiretroviral drugs from four different classes: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and inhibitors of virus-cell fusion. Increasing resistance against antiretroviral drugs calls for the development of new compounds and drug classes. The growing understanding of molecular mechanisms in HIV-replication led to the identification of further steps which might serve as novel antiretroviral targets. Uninfected cells could be protected from HIV by inhibiting extracellular binding mechanisms. Improvement of existing antiretroviral drugs and further development of novel therapeutic targets will enrich antiretroviral treatment.
    No preview · Article · Sep 2005 · Der Internist