Inadequate Erythropoietin Response to Anaemia in HIV Patients: Relationship to Serum Levels of Tumour Necrosis Factor-Alpha, Interleukin-6 and Their Soluble receptors

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r  = −0.54; P  < 0.001; sTNF-R II: r  = −0.47; P  < 0.001) as well as interleukin-6 levels ( r  = −0.29; P  < 0.001). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II ( P  < 0.001). The results of this study suggest that similar to its action in vitro , activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-α, this activation is particularly reflected by elevations of soluble TNF receptor levels.     

The impact of performance uncertainty on the postimperative negative variation

In a delayed matching-to-sample task, the impact of clear or ambiguous go versus clear no-go signals on the post-imperative negative variation (PINV) was examined in 11 patients with a chronic schizophrenic disorder (DSM-III-R) and in a control group of 13 healthy subjects matched to the patient sample by age, sex, and education. Size and spatial position of a visual S2 had to be matched to one of two visual patterns in the S1 presented 4 s earlier. In 96 trials, the S2 was identical in size with one of the two patterns of S1 (clear matching). These trials varied pseudorandomly, with 60 trials in which the S2 was of intermediate size. On a randomly interspersed additional 48 trials, an S2 differing in color and shape signaled no-go. The electroencephalogram was recorded from Fz, Cz, Pz, F3, F4, C3, C4, P3, and P4. Although groups did not differ in contingent negative variation amplitude the PINV was generally more pronounced in patients than in controls. In both groups, ambiguity of the to-be-matched S2 produced larger PINV amplitudes; the no-go signal elicited only a small PINV. Differential effects of ambiguity and no-go on PINV amplitude and its scalp distribution suggest that “performance” and “action” uncertainty contribute to PINV generation and that thresholds for both effects are reduced in schizophrenics.     

Correlation of transient elastography with APRI and FIB‐4 in a cohort of patients with congenital bleeding disorders and HCV or HIV/HCV coinfection

Summary. Patients with inherited bleeding disorders frequently suffer from chronic hepatitis C virus (HCV) mono‐ or human immunodeficiency virus (HIV)/HCV coinfection. Non‐invasive markers for liver fibrosis are warranted for these patients. We tested a large cohort of haemophilic patients with HCV mono‐ or HIV/HCV coinfection for correlation of transient elastography (TE) with two simple surrogate markers of liver fibrosis and for differences in fibrosis stages according to these markers. We prospectively enrolled HCV‐positive patients with congenital bleeding disorders with or without HIV coinfection. Liver function tests and platelet counts were determined and TE was performed. Aspartate aminotransferase‐to‐platelet ratio index (APRI) and a simple index called FIB‐4 were calculated and results were correlated with TE. A total number of 174 patients were included (23% HCV, 36% HIV/HCV coinfected, 33% with cleared HCV and 8% with ongoing HIV but cleared HCV). TE correlated significantly with APRI and FIB‐4 (r = 0.60; P < 0.001 and r = 0.54; P < 0.001 respectively). This correlation was pronounced in patients with ongoing HCV infection (r = 0.67; P < 0.001 and r = 0.60; P < 0.001). Prediction of advanced fibrosis resulted in concordance rates >80% with combinations of TE plus APRI and APRI plus FIB‐4. HIV/HCV coinfected patients did not present with advanced fibrosis stages when compared with HCV‐monoinfected patients. Combinations of two non‐invasive markers may significantly reduce the number of liver biopsies in patients with bleeding disorders and advanced liver fibrosis. Furthermore, our data support previous studies that observed a favourable outcome in patients with HIV/HCV and a preserved immune function in times of highly active antiretroviral therapy.     

The IL-1 system in HIV infection: peripheral concentrations of IL-1β, IL-1 receptor antagonist and soluble IL-1 receptor type II

The proinflammatory cytokine IL-1β is thought to be involved in ongoing HIV disease. Furthermore, its naturally occurring inhibitors soluble IL-1 receptor type II (sIL-1RII) and IL-1 receptor antagonist (IL-1Ra) may play a pivotal role in regulating its biological action. To investigate the involvement of the IL-1 system we determined serum levels of IL-1β, IL-1Ra and sIL-1RII in 90 HIV⁺ patients. The obtained values were compared with markers of disease progression such as CD⁺ count, 5′-neopterin, β₂-microglobulin and soluble tumour necrosis factor receptors (sTNF-R) p55 and p75 and then compared with C-reactive protein (CRP), granulocyte count, lL-6 and TNF-α. While IL-1Ra concentrations increased significantly with progressive CDC disease stages, sIL-1RII and IL-1β were not altered in our cohort. IL-1Ra showed statistical relation to decreasing CD4⁺ lymphocytes and increasing 5′-neopterin, β₂-microglobulin, sTNF-R p55, sTNF-R p75. Furthermore, IL-1Ra correlated positively with serum IL-6, TNF-α, CRP and granulocytes. In contrast, sIL-1RII and IL-1β tended to show an inverse correlation or showed no significant relationship to all these parameters. Il-1β was measurable only in a limited number of samples. IL-1Ra showed a clear relationship to acute inflammatory events as well as to the different disease stages. Our data suggest a dissociation between IL-1Ra and sIL-1RII serum levels which may indicate that the two IL-1 binding proteins have different pathophysiological roles in HIV infection.