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1.
BMC Infect Dis ; 20(1): 882, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238950

RESUMO

BACKGROUND: Altered fat distribution and chronic inflammation are found in both persons living with HIV (PLWH) and persons with diabetes mellitus type 2 (DM2) and are known risk factors for cardiovascular diseases (CVD). We aimed to investigate if a synergistic effect of HIV infection and DM2 was found on fat distribution and inflammation. METHODS: A cross-sectional study was performed including PLWH with HIV RNA < 200 copies/mL (18 with DM2 (HIV + DM2+), 18 without DM2 (HIV + DM2-)) and controls (19 with DM2 (controls with DM2) and 25 without DM2 (healthy controls). We measured fat distribution using dual-energy X-ray absorptiometry scan. Plasma concentrations of adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF- α) and soluble CD14 (sCD14) was measured using snap-frozen plasma. RESULTS: HIV + DM2+ and HIV + DM2- had comparable trunk/limb fat ratio. In contrast, HIV + DM2+ had a higher trunk/ limb fat ratio than controls with DM2 and healthy controls (p = 0.013 and p < 0.001, respectively). However, HIV + DM2+ and controls with DM2 had comparable amount of trunk fat mass (kg) (p = 0.254). A lower concentration of plasma adiponectin and higher concentration of IL-6 was found in HIV + DM2+ than in HIV + DM2-(p = 0.037 and p = 0.039) and in healthy controls (p = 0.001 and p = 0.012). In contrast, plasma adiponectin and IL-6 concentrations were comparable in HIV + DM2+ and controls with DM2 (p = 0.345 and p = 0.825). Concentration of sCD14 was comparable in HIV + DM2+ and HIV + DM2-(p = 0.850), but elevated in HIV + DM2+ compared to controls with DM2 (p < 0.001) and healthy controls (p = 0.007). No statistical interactions were found between HIV infection and DM2 for any of the depending variables. CONCLUSION: A synergistic effect of HIV and DM2 was not found for any of the outcomes. However, HIV + DM2+ had features related to both HIV infection and DM2 with a high trunk/limb ratio, high trunk fat mass, low concentration of plasma adiponectin and elevated concentrations of IL-6 and sCD14. This could contribute to elevated risk of CVD.


Assuntos
Adiponectina/sangue , Distribuição da Gordura Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Infecções por HIV/sangue , Infecções por HIV/complicações , HIV/genética , Absorciometria de Fóton , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Estudos Transversais , Feminino , Infecções por HIV/virologia , Humanos , Interleucina-6/sangue , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue
2.
Sci Rep ; 8(1): 6725, 2018 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-29712976

RESUMO

HIV infection and type 2 diabetes are associated with altered gut microbiota, chronic inflammation, and increased cardiovascular risk. We aimed to investigate the combined effect of these diseases on gut microbiota composition and related metabolites, and a potential relation to endothelial dysfunction in individuals with HIV-infection only (n = 23), diabetes only (n = 16) or both conditions (n = 21), as well as controls (n = 24). Fecal microbiota was analyzed by Illumina sequencing of the 16 S rRNA gene. Markers of endothelial dysfunction (asymmetric dimethylarginine [ADMA]), tryptophan catabolism (kynurenine/tryptophan [KT]-ratio), and inflammation (neopterin) were measured by liquid chromatography-tandem mass spectrometry. The combination of HIV and type 2 diabetes was associated with reduced gut microbiota diversity, increased plasma KT-ratio and neopterin. Microbial genes related to tryptophan metabolism correlated with KT-ratio and low alpha diversity, in particular in HIV-infected with T2D. In multivariate analyses, KT-ratio associated with ADMA (ß = 4.58 [95% CI 2.53-6.63], p < 0.001), whereas microbiota composition per se was not associated with endothelial dysfunction. Our results indicate that tryptophan catabolism may be related to endothelial dysfunction, with a potentially detrimental interaction between HIV and diabetes. The potential contribution of gut microbiota and the impact for cardiovascular risk should be further explored in prospective studies powered for clinical end points.


Assuntos
Doenças Cardiovasculares/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/genética , Infecções por HIV/microbiologia , Inflamação/microbiologia , Arginina/análogos & derivados , Arginina/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Endotélio/metabolismo , Endotélio/microbiologia , Endotélio/patologia , Fezes/microbiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/genética , Infecções por HIV/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Cinurenina/metabolismo , Masculino , Metabolismo/genética , Pessoa de Meia-Idade , Neopterina/metabolismo , RNA Ribossômico 16S/genética , Fatores de Risco , Triptofano/metabolismo
3.
J Acquir Immune Defic Syndr ; 77(2): 217-220, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040164

RESUMO

BACKGROUND: HIV persists in a latent state in quiescent CD4 T cells preventing eradication of HIV. CD52 is a surface molecule modulated by HIV. We aimed at examining factors related to CD52 expression on CD4 T cells in HIV-positive individuals and the impact of initiation of combination antiretroviral therapy (cART). METHODS: Peripheral blood mononuclear cells from 18 HIV-positive individuals and 10 uninfected age- and sex-matched controls were examined by flow cytometry for CD38 and CD52 expression on CD4 T cells. Stimulation assays were performed on 8 healthy blood donors to determine a cutoff for CD52 expression. RESULTS: All examined CD4 T cells expressed CD52. However, both CD4 T cells with higher (CD52) and with lower CD52 expression (CD52dim) were found in HIV-positive individuals compared to uninfected controls. Two % CD52dim cells defined groups of high and low CD52: the group of individuals with high CD52 had higher CD4 counts at baseline (447 vs. 54 cells/µL, P = 0.02) and higher increase in CD4 counts during follow-up compared with low CD52 (P = 0.02). After 12 months of cART, CD52 increased (median fluorescence intensity 4846 vs. 5621, P < 0.05), whereas CD38 decreased (median fluorescence intensity 1519 vs. 730, P < 0.0001). CONCLUSIONS: All HIV-positive individuals in this cohort had CD4 T cells that expressed CD52. Higher CD4 counts were found in those with high CD52. Furthermore, an increase in CD52 was found after 12 months of cART, indicating that anti-CD52 antibodies may be more efficient for depletion of CD4 T cells in HIV-positive individuals on cART.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos/química , Antígeno CD52/análise , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , ADP-Ribosil Ciclase 1/análise , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Glicoproteínas de Membrana/análise
4.
BMC Infect Dis ; 17(1): 262, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28399815

RESUMO

BACKGROUND: By assessing the changes in concentration of soluble receptor activator of nuclear factor κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. METHODS: We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation. RESULTS: Soluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL. CONCLUSION: In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART. TRIAL REGISTRATION: Clinical-Trial.gov . id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Ligante RANK/metabolismo , Adulto , Linfócitos T CD4-Positivos , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade
5.
BMC Infect Dis ; 17(1): 234, 2017 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-28356058

RESUMO

BACKGROUND: Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD. METHODS: Cross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA <200 copies/mL (n = 25 with T2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28 without T2D (HIV-T2D-)). Groups were matched on age and sex. High sensitive C-reactive protein (hsCRP) was used to determine inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine-N-oxide (TMAO), a microbiota-dependent, pro-atherogenic marker was measured using stable isotope dilution LC/MS/MS. RESULTS: The percentage of HIV + T2D+, HIV + T2D-, HIV-T2D+, and HIV-T2D- with hsCRP above cut-off was 50%, 19%, 47%, and 11%, respectively. HIV + T2D+ had elevated ADMA (0.67 µM (0.63-0.72) compared to HIV + T2D- (0.60 µM (0.57-0.64) p = 0.017), HIV-T2D+ (0.57 µM (0.51-63) p = 0.008), and HIV-T2D- (0.55 µM (0.52-0.58) p < 0.001). No differences in TMAO between groups were found. However, a positive correlation between ADMA and TMAO was found in the total population (rs = 0.32, p = 0.001), which was mainly driven by a close correlation in HIV + T2D+ (rs = 0.63, p = 0.001). CONCLUSION: Elevated inflammation and evidence of endothelial dysfunction was found in HIV-infected persons with T2D. The effect on inflammation was mainly driven by T2D, while both HIV infection and T2D may contribute to endothelial dysfunction. Whether gut microbiota is a contributing factor to this remains to be determined.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Infecções por HIV/fisiopatologia , Inflamação/etiologia , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Masculino , Metilaminas/sangue , Pessoa de Meia-Idade , Fatores de Risco , Espectrometria de Massas em Tandem
6.
Scand J Gastroenterol ; 51(11): 1387-97, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27436030

RESUMO

The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion and impairment of cytotoxic function of HCV-specific T cells and NK cells are found in patients with chronic HCV infection. In contrast, an increase in immune regulatory functions is found primarily in form of increased IL-10 production possibly due to increased level and function of anti-inflammatory Tregs. Thus, the major immune players during chronic HCV infection are characterized by a decrease of cytotoxic function and increase of inhibitory functions. This may be an approach to diminish intrahepatic and systemic inflammation. Finally, there has been increasing awareness of regulatory functions of epigenetic changes in chronic HCV infection. A vast amount of studies have revealed the complexity of immune regulation in chronic HCV infection, but the interplay between immune regulation in virus and host remains incompletely understood. This review provides an overview of regulatory functions of HCV-specific T cells, NK cells, Tregs, IL-10, and TGF-ß, as well as epigenetic changes in the setting of chronic HCV infection.


Assuntos
Imunidade Adaptativa , Hepatite C Crônica/imunologia , Células Matadoras Naturais/imunologia , Cirrose Hepática/virologia , Linfócitos T Reguladores/imunologia , Hepacivirus , Hepatite C Crônica/complicações , Humanos , Interleucina-10/imunologia , Cirrose Hepática/imunologia , MicroRNAs/metabolismo , Fator de Crescimento Transformador beta/imunologia
7.
PLoS One ; 8(5): e63744, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23696852

RESUMO

BACKGROUND: HIV-infected controllers control viral replication and maintain normal CD4+ T cell counts. Long Term Non-Progressors (LTNP) also maintain normal CD4+ T cell counts, but have on-going viral replication. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell counts in controllers and LTNP. METHODS: 25 HIV-infected controllers and 14 LTNP were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Production and destruction of T cells were addressed by determination of T cell receptor excision circles (TREC), recent thymic emigrants, naïve cells, immune activation, senescence and apoptosis. Furthermore, telomere length was determined, and the amount of lymphoid tissue in tonsil biopsies was quantified. RESULTS: Controllers presented with partly preserved thymic output, preserved expression of the IL-7 receptor and IL-7 receptor density, and lower levels of destruction of cells than progressors resembling HIV-negative healthy controls. In contrast, LTNP appeared much like progressors, and different from controllers in immune activation, senescence, and apoptosis. Interestingly, CD8+ RTE, TREC and telomere length were partly preserved. Finally, both controllers and LTNP displayed decreased amounts of lymphoid tissue compared to healthy controls. CONCLUSIONS: Controllers presented with an immunological profile different from LTNP. While controllers resembled healthy controls, LTNP were similar to progressors, suggesting different immunological mechanisms to be responsible for preserved CD4+ T cell counts in LTNP and controllers. However, both controllers and LTNP presented with reduced amounts of lymphoid tissue despite preserved CD4+ T cell counts, indicating HIV to cause damage even in non-progressors.


Assuntos
Infecções por HIV/imunologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos Transversais , Feminino , Citometria de Fluxo , Infecções por HIV/genética , Soropositividade para HIV , Humanos , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/imunologia , Telômero/genética , Carga Viral
8.
AIDS ; 27(4): 659-62, 2013 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-23135168

RESUMO

CD8 Tc17 cells with pro-inflammatory properties have only recently been acknowledged, and Tc17 cells in HIV-infection are not described. CD3CD8CD161 Tc17 cells and the production of interleukin (IL)-17 were examined in untreated and treated HIV-infected patients, HIV-hepatitis C virus co-infected patients, and healthy controls. Depletion of CD3CD8CD161 Tc17 cells and diminished production of IL-17 in HIV-infected patients were found. The level of Tc17 cells was associated with the CD4 cell count in treated patients.


Assuntos
Complexo CD3/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , Hepatite C Crônica/imunologia , Interleucina-17/imunologia , Adulto , Contagem de Linfócito CD4 , Coinfecção , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Replicação Viral
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