Short communication high risk of endothelial dysfunction in HIV individuals may result from deregulation of circulating endothelial cells and endothelial progenitor cells.

Endothelial progenitor cells (EPC) and circulating endothelial cells (CEC) have recently been considered as biomarkers of cardiovascular risk (CVDR) in healthy subjects. The impact of HIV infection on these cells is not well known. A case-control study was conducted in 15 antiretroviral-naive HIV(+) patients and 15 HIV-negative controls. The quantitative profile of CEC and EPC differed significantly in HIV(+) and HIV(-) subjects. HIV(+) subjects had significantly more CEC and less EPC than HIV(-) controls. A quantitative impairment in the balance of the CEC and EPC might contribute to the increased subclinical CVDR in HIV(+) patients.

The expansion ability but not the quality of HIV-specific CD8(+) T cells is associated with protective human leucocyte antigen class I alleles in long-term non-progressors.

Studies in long-term non-progressors (LTNP) have suggested that the quality of the CD8(+) response may involve protective human leucocyte antigen (HLA) class I alleles. However, studies examining the expansion ability of different functional CD8(+) T cells and their association with HLA class I alleles are lacking. LTNP, untreated typical progressors (TP) and patients successfully on highly active retroviral therapy (HAART) during 1 year (HP) were included. HLA class I typing was performed using a sequence-specific primer assay. Functional subsets of Gag- and Nef-specific CD8(+) cells were analysed based on the production of macrophage inflammatory protein (MIP)-1ß, tumour necrosis factor (TNF)-α and interleukin (IL)-2. Their expansion abilities were evaluated after 10-day culture in the presence of Gag and Nef human immunodeficiency virus (HIV) peptides. No differences were seen when comparing quantitative and qualitative HIV-specific CD8(+) T cell responses according to the presence/absence of protective HLA alleles (B*58 and B*27 supertypes) in each group. However, LTNP with protective HLA alleles showed a higher expansion ability of Gag-specific MIP(+) TNF(+) IL-2(+) T cells and Nef-specific MIP(+) TNF(+) IL-2(+) . HLA-B*5701+LTNP displayed a higher expansion ability of Gag and Nef-specific MIP(+) TNF(-) IL-2(+) T cells than HLA-B*5701-LTNP. This was not so for HLA-B*2705. No differences were seen in the expansion ability according to the presence/absence of protective HLA alleles in TP and HP. The expansion ability of polyfunctional CD8(+) T cells is modulated by HLA class I alleles and targeted protein. LTNP with HLA class I protective alleles (mainly B*5701) display better expansion ability of polyfunctional HIV-specific CD8(+) T cells than the rest, suggesting that factors other than HLA-B*5701 must contribute to the control of viral replication in other LTNP. Furthermore, these attributes of HIV-specific CD8(+) T are not restored by HAART; thus, adjuvant therapies and vaccines that induce and/or normalize the expansion ability of HIV-specific T cells are required.

HCV-specific T-cell responses in HIV/hepatitis C virus-coinfected patients on highly active antiretroviral therapy are comparable to those observed in hepatitis C virus-monoinfected individuals.

BACKGROUND: Cellular responses against hepatitis C virus (HCV) are impaired in HIV/HCV-coinfected patients showing uncontrolled viral replication and immune suppression. Very few studies have explored to what extent HCV-specific response improves as a consequence of control of HIV replication by highly active antiretroviral therapy. We compared HCV-specific T-cell responses between HIV/HCV-coinfected patients, showing complete viral suppression, and HCV-monoinfected patients. METHODS: HCV-specific T-cell responses were examined in 50 interferon-naive patients with chronic hepatitis C: 27 HCV-mono-infected and 23 HIV/HCV-coinfected on highly active antiretroviral therapy and undetectable HIV load. Production of interferon-γ and tumor necrosis factor-α was simultaneously measured in response to genotype-matched overlapping peptides spanning the whole HCV proteome by flow cytometry. Differences between groups were tested using nonparametric tests. RESULTS: More than half of patients presented CD4+ (60%) or CD8+ (57%) response to at least one HCV protein with no significant differences between both groups. Intensity and breadth of response were also similar between groups. The functional profile of response was represented, in both groups, mainly by monofunctional subsets, although there were some differences between CD4+ and CD8+ T-cell response. CD8+ response was mediated almost exclusively by monofunctional interferon-γ+ cells, whereas bifunctional interferon-γ+ tumor necrosis factor-α+ cells showed a moderate contribution to CD4+ response. Most of the CD8+ response was mediated by interferon-γ, whereas tumor necrosis factor-α was the highest contributor to CD4+ response. CONCLUSIONS: Our study demonstrates that in HIV/HCV-coinfected patients with maximal HIV suppression under highly active antiretroviral therapy, several characteristics of anti-HCV T-cell response are similar to those found in HCV-monoinfected patients, suggesting that control of HIV replication might improve HCV-specific T-cell response in HIV/HCV-coinfected patients.

Hemofilia: ejercicio y deporte / Haemophilia: exercise and sport

El ejercicio físico y el deporte constituyen uno de los pilares básicos en el tratamientode la hemofilia. Este trabajo describe un resumen de las características de la hemofiliay, a través de una exhaustiva revisión bibliográfica, se analiza la importancia de la condiciónfísica, en relación con la prevención y el tratamiento de las lesiones musculoesqueléticas en elpaciente hemofílico.La hemofilia es una enfermedad hematológica hereditaria, con lesiones ortopédicas características.Afecta a individuos varones y presenta un déficit de factores de la coagulación queprovoca hemorragias incluso espontáneas (en pacientes graves sin tratamiento). Las lesionesmás frecuentes son: hemartrosis, sinovitis, hematomas musculares y artropatía hemofílica. Lacondición física del paciente hemofílico, instrumentada mediante terapia sustitutiva de factoresde la coagulación, es fundamental y requiere fisioterapia, ejercicio físico y deporte.Basándonos en las recomendaciones de los comités de expertos de la Federación Mundial deHemofilia (WFH) y utilizando las principales bases de datos, mediante estrategias de búsquedacon palabras clave, se obtuvieron 756 referencias, de las que tan sólo 74 superaron los criteriosde inclusión.Las publicaciones se agruparon por áreas temáticas, diferenciando artículos de revisión,trabajos observacionales y experiencias clínicas, estudios experimentales y actuaciones intervencionistassobre parámetros concretos de la condición física.Se concluye con la evidencia de la importancia de la recomendación del ejercicio físico ydeporte en la hemofilia, el consenso en su idoneidad para el bienestar físico, psíquico y socialde los pacientes, y la necesidad de incrementar los trabajos científicos al respecto(AU)

Physical exercise and sports is one of the basic foundations in the treatment of haemophilia.This article gives a brief description of the characteristics of haemophilia, and throughan exhaustive literature review, the importance of the physical condition, as regards preventionand treatment of musculoskeletal lesions in the haemophilic patient, is also analysed.Haemophilia is a hereditary haematological disease, characteristic orthopaedic lesions. Itaffects males and has a deficiency of clotting factors which causes haemorrhages, includingspontaneous (in severe patients without treatment). The most common lesions are: haemarthrosis,synovitis, muscle haematomas and haemophilic arthritis. The physical condition of thehaemophilic patient, controlled by clotting factor replacement therapy, is fundamental andrequires physiotherapy, physical exercise and sport.Based on the recommendations by expert committees of the World Haemophilia Foundation(WFH) and using major data bases and search strategies with key words, 756 references wereobtained, of which on 74 passed the inclusion criteria.The publications were grouped by subject area, differentiating review articles, observationalstudies and clinical experiences, experimental studies and interventionist actions on specificparameters of physical condition.It concludes with important evidence on the recommendation of physical exercise and sportin haemophilia, the consensus on its suitability for the physical and social wellbeing of thepatients and the need to increase scientific works in this respect(AU)

Low-level exposure to HIV induces virus-specific T cell responses and immune activation in exposed HIV-seronegative individuals.

HIV-specific T cells response and T cell activation are frequently seen in exposed seronegative individuals (ESN). In this study, we report HIV-specific response and level of T cell activation in ESN partners of HIV-infected patients presenting low or undetectable levels of HIV-RNA. We evaluated 24 HIV-serodiscordant couples. ESN were classified into three categories of exposure to HIV (very low, low, and moderate-high), considering levels of HIV-RNA in their infected partner and frequency of sexual high-risk practices within the last 12 mo. HIV-specific T cell responses and activation levels in T cell subsets were evaluated by flow cytometry. We reported that 54% of ESN had detectable HIV-specific T cells response, being the highest prevalence seen in the low exposure group (64%). Several T cell subsets were significantly increased in ESN when compared with controls: CD4(+)CD38(+) (p = 0.006), CD4(+)HLA-DR(-)CD38(+) (p = 0.02), CD4(+)CD45RA(+)CD27(+)HLA-DR(-)CD38(+) (p = 0.002), CD8(+)CD45RA(+)CD27(+)CD38(-)HLA-DR(+) (p = 0.02), and CD8(+)CD45RA(+)CD27(-)CD38(+)HLA-DR(+) (p = 0.03). Activation of CD8(+) T cells was increased in ESN with detectable HIV T cell responses compared with ESN lacking these responses (p = 0.04). Taken together, these results suggest that persistent but low sexual HIV exposure is able to induce virus-specific T cells response and immune activation in a high proportion of ESN, suggesting that virus exposure may occur even in conditions of maximal viral suppression in the HIV-infected partner.