RESUMEN
PURPOSE: Non-dipping nocturnal blood pressure (BP) pattern has been reported prevalent among HIV-infected patients and is associated with adverse cardiovascular outcomes. The aims of this observational study were to identify predictors of nocturnal BP decline, and to explore whether diurnal BP profile is associated with alterations in cardiac structure and function. MATERIALS AND METHODS: A total of 108 treated HIV-infected patients with suppressed viremia underwent ambulatory BP measurement, 51 of these patients also underwent echocardiography. RESULTS: Non-dipping nocturnal BP pattern was present in 51% of the patients. Decreased nocturnal decline in systolic BP (SBP) correlated with lower CD4 count (rsp = 0.21, p = 0.032) and lower CD4/CD8 ratio (rsp = 0.26, p = 0.008). In multivariate linear regression analyses, lower BMI (p = 0.015) and CD4/CD8 ratio <0.4 (p = 0.010) remained independent predictors of nocturnal decline in SBP. Nocturnal decline in SBP correlated with impaired diastolic function, e' (r = 0.28, p = 0.049) as did nadir CD4 count (rsp = 0.38, p = 0.006). In multivariate linear regression analyses, nadir CD4 count <100 cells/µL (p = 0.037) and age (p < 0.001) remained independent predictors of e'. CONCLUSIONS: Compromised immune status may contribute to attenuated diurnal BP profile as well as impaired diastolic function in well-treated HIV infection.
Asunto(s)
Presión Sanguínea , Infecciones por VIH/fisiopatología , Corazón/fisiopatología , Adulto , Biomarcadores/análisis , Monitoreo Ambulatorio de la Presión Arterial , Relación CD4-CD8 , Ritmo Circadiano , Diástole , Femenino , Infecciones por VIH/complicaciones , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Antiretroviral therapy (ART) to suppress HIV replication has reduced morbidity and mortality yet effectiveness of current HIV drugs is threatened by HIV drug resistance (HIVDR) mutations. OBJECTIVE: To determine HIVDR mutations using proviral DNA from specimens of patients presenting to an HIV treatment clinic. METHODS: DNA from 103 patients, 86 treatment-experienced, 17 treatment-naïve, were genotyped for the HIV-1C reverse transcriptase gene (RT; codons 21-304) using Sanger sequencing and sequences analyzed using Sequencher software. Resistance mutations were interpreted using Stanford HIVDR reference database. RESULTS: Median age was 39 (IQR, 33-46) years and 80% of patients were female. Six-percent (n=6) had at least one HIVDR mutation, comprising NRTI-associated mutations, (M184V, T69D, T69N and V75I); NNRTI-associated mutations (G190A, K103N, V106M, Y181C) and thymidine analogue associated mutations (D67N, K70R, K219Q, L210W, M41L, T215Y). Of the six participants, with at least one HIVDR mutation, all were treatment experienced, five were on tenofovir, lamivudine and nevirapine and one was on tenofovir, lamivudine and atazanavir. There was no difference in median CD4 count and viral loads when patients were compared by presence of HIVDR mutations. CONCLUSION: We demonstrated the use of proviral DNA in HIVDR testing in adult patients and present that all the patients with various kinds of HIVDR mutations were treatment experienced, pointing to the role of drug regimens in driving viral mutations. Thus, the use of proviral DNA has potential to help provide surveillance on risk of HIVDR in HIV-infected individuals who are on treatment, which may assist in corrective treatment.
RESUMEN
BACKGROUND: Recent evidence suggests that HIV infection, even with treatment, increases the risk of coronary heart disease (CHD) and that both chronic inflammation and traditional risk factors play key roles in HIV-associated CHD. SUBJECTS AND METHODS: Patients (N=152), attending Harare HIV clinic, 26% of them male and 82% of them on antiretroviral therapy (ART), were studied. Inflammatory markers comprising of cytokines such as pro-inflammatory tumor necrosis factor-α, (TNF-α), anti-inflammatory interleukin 10, (IL-10) and highly sensitive C reactive protein (hsCRP) together with lipids were assayed using enzyme linked immunosorbent assay (ELISA), immuno-turbidimetric and enzymatic assays, respectively. Correlation analysis of inflammatory markers versus lipid profiles was carried out using bivariate regression analysis. RESULTS: Anti-inflammatory cytokine IL-10 and inflammatory hsCRP levels were elevated when measured in all the HIV positive patients, while TNF-α and lipid levels were within normal ranges. Pro-inflammatory TNF-α was significantly higher in ART-naive patients than ART-experienced patients, whereas the reverse was observed for anti-inflammatory IL-10 and anti-atherogenic HDL-C. Correlation analysis indicated a significant positive linear association between IL-10 and total cholesterol (TC) levels but no other correlations were found. CONCLUSION: High cytokine ratio (TNF-α/IL-10) indicates higher CHD risk in ART-naive patients compared to the ART-exposed. The CHD risk could be further strengthened by interplay between inflammatory markers and high prevalence of low HDL-C. Lack of correlation between pro-inflammatory markers (hsCRP and TNF-α) with lipid fractions and correlation between anti-inflammatory IL-10 with artherogenic TC were unexpected findings, necessitating further studies in future.
RESUMEN
The open window theory indicates altered immunity 3 to 72 hours after exercise. The J-curve describes the risk of illness in response to exercise. The aim of this study was to examine the secretion of proinflammatory and anti-inflammatory cytokines before and after long-term strenuous exercise. Fourteen marathon and 16 half-marathon runners and 10 military cadets participating in a military ranger-training course were recruited to this study. Within-subject design was used measuring levels of plasma cytokines before, during, and after exercise. Plasma cytokines were measured using Luminex multiplex technology and ELISA. Comparing pre/post plasma levels both the marathon- and the half-marathon runners showed heavily increased levels of IL-6, IL-10, and IL-8 (P < 0.001). LPS stimulation among the half-marathon runners decreased the postrace levels of IL-6, IL-1b, and TNFα by 45%, 24%, and 43%, respectively (P < 0.01). During the ranger training course the spontaneous and LPS-stimulated levels of IL-6, IL-8, IL-10, IL-1b, and TNFα changed in a similar fashion as in the half-marathon runners although the fluctuations were smaller. Our study supports the open window and the J-curve theory; the immune system is more activated and the subjects are more threatened to infectious pathogens after intensive physical activity and in the period after exercise.
RESUMEN
HIV infection, together with ART, is associated with changes in biochemical, metabolic parameters and lipid profiles. The aim of this study was to compare changes in lipid profiles among HIV positive outpatients over nine months. 171 patients were investigated, 79% were ART experienced, and 82% of ART experienced patients were on NVP/EFV first line at baseline, but some patients changed ART groups over follow-up and classification was based on intent to treat. More than 60% ART naïve and ART experienced patients had some form of dyslipidemia either at baseline or at follow-up, but mean lipid values for the two groups were within normal limits. At baseline and follow-up, mean levels of TC and HDL were slightly higher in the ART experienced group. Interestingly, there was higher increase in HDL over time in the ART negative group compared to the ART positive group. There was a decrease in TC/HDL ratio in both groups over time, suggesting a reduction in calculated risk of CHD over time. HIV positive patients frequently show various forms of dyslipidemia, but there are no changes in average atherogenic lipid levels and results suggest reduced risk of CHD, mainly due to increases in HDL, after nine months of observation time.
RESUMEN
BACKGROUND: Carnitine plays an essential role in fatty acid metabolism, exerts substantial antioxidant action and regulates immune functions. We hypothesized that a disturbed carnitine metabolism could be involved in progression of HIV infection. MATERIALS AND METHODS: Plasma levels of L-carnitine, its precursors, and short-, medium- and long-chain acylcarnitines were analysed with HPLC/mass spectrometry in HIV-infected patients with various disease severities including patients who acquired Mycobacterium avium complex (MAC) infection. In vitro, we examined the MAC-purified protein derivate (PPD)-induced release of TNF-α and IFN-γ in peripheral blood mononuclear cells (PBMCs) from patients with either high or low plasma levels of acylcarnitines. RESULTS: Plasma levels of the short-chain (e.g. propionyl-carnitine) and medium-chain (e.g. octanoyl-carnitine) acylcarnitines were reduced in patients with advanced HIV infection. These acylcarnitines gradually decreased in rapid progressors, while minimal changes were observed in the nonprogressors. Plasma levels of propionyl-carnitine and octanoyl-carnitine significantly increased during antiretroviral therapy (ART). However, ART did not restore levels to those observed in healthy controls. Depletion of propionyl-carnitine and octanoyl-carnitine was observed prior to MAC infection, and the release of TNF-α and IFN-γ from PBMC was decreased after stimulation with MAC-PPD in samples from HIV-infected patients with low levels of propionyl-carnitine or octanoyl-carnitine. CONCLUSIONS: Our findings suggest an association between disturbed acylcarnitine metabolism, immune dysregulation and disease progression in HIV-infected patients. Low levels of propionyl-carnitine and octanoyl-carnitine were associated with increased susceptibility to MAC infection in HIV patients with advanced disease.
Asunto(s)
Carnitina/análogos & derivados , Carnitina/sangre , Infecciones por VIH/sangre , Infección por Mycobacterium avium-intracellulare/sangre , Adulto , Terapia Antirretroviral Altamente Activa , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Interferón gamma , Ensayos de Liberación de Interferón gamma , Estudios Longitudinales , Masculino , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/complicaciones , Factor de Necrosis Tumoral alfaAsunto(s)
Albuminuria/sangre , Infecciones por VIH/complicaciones , Lipocalinas/sangre , Proteínas Proto-Oncogénicas/sangre , Proteínas de Fase Aguda , Adulto , Biomarcadores/sangre , Femenino , Infecciones por VIH/sangre , Humanos , Enfermedades Renales/diagnóstico , Lipocalina 2 , Masculino , Persona de Mediana EdadRESUMEN
Soluble proteins that bind LPS, like myeloid differentiation-2 (MD-2) and CD14, have essential roles in regulating LPS signaling through TLR4. During a gram-negative bacterial infection, the host may control the response by adjusting the levels of soluble MD-2 and CD14. To address the surface expression of MD-2 on human leukocytes, we developed a mAb, IIC1, that recognized MD-2 both free and when bound to TLR4. MD-2 was found on the surface of freshly isolated monocytes, on a subpopulation of CD19(+) B-cells and on CD15(+) neutrophils. LPS transiently reduced the MD-2 levels on monocytes, which is most likely due to endocytosis of the LPS receptor complex since MD-2 colocalized with TLR4 in early endosomes after LPS stimulation. In the absence of LPS, MD-2 partly colocalized with TLR4 in Golgi trans and medial compartments. Cultivating monocytes for 18-20 h resulted in loss of MD-2 expression on the surface, which was reversed either by LPS or IL-10. Furthermore, addition of IL-10, but not LPS, resulted in a considerable increase in mRNA for both MD-2 and CD14. Using ELISA, we demonstrated that IL-10 had a profound dose- and time-related effect on the release of soluble MD-2 and soluble CD14 from monocytes. In HIV-infected patients, the amounts of MD-2, CD14, and IL-10 increased significantly in the patient group with AIDS. Of interest, we found that IL-10, CD14, and MD-2 levels were positively correlated, suggesting that IL-10 may be a driving force for increased release of MD-2 and CD14 during systemic inflammation.
Asunto(s)
Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Interleucina-10/fisiología , Receptores de Lipopolisacáridos/biosíntesis , Antígeno 96 de los Linfocitos/biosíntesis , Monocitos/inmunología , Monocitos/metabolismo , Regulación hacia Arriba/inmunología , Adulto , Animales , Anticuerpos Monoclonales/metabolismo , Sitios de Unión de Anticuerpos , Células CHO , Línea Celular , Cricetinae , Cricetulus , Femenino , Humanos , Mediadores de Inflamación/fisiología , Interleucina-10/sangre , Receptores de Lipopolisacáridos/sangre , Receptores de Lipopolisacáridos/genética , Antígeno 96 de los Linfocitos/sangre , Antígeno 96 de los Linfocitos/genética , Masculino , Ratones , Ratones Endogámicos BALB C , ARN Mensajero/biosíntesisRESUMEN
Abscess of the psoas muscle is an infrequent diagnosis at hospitals in Northern countries. We report on 16 patients who had this diagnosis during the period 1991-2001. Eight patients were immigrants who had previously been healthy and most of them had experienced symptoms for approximately 1 y. MRI or CT scans revealed spondylodiscitis in 6 of these patients and Mycobacterium tuberculosis was identified as the causative agent. With the exception of 1 patient who was exclusively treated with antituberculous agents, all 8 immigrant patients were successfully treated with antituberculous agents in addition to percutaneous drainage. The other 8 patients were Norwegians, 4 of whom had underlying conditions such as diabetes mellitus or drug abuse. The causative microorganisms were Staphylococcus aureus or Streptococcus spp., with the exception of M. tuberculosis in 1 case. The Norwegian patients had a more acute history of symptoms than the immigrant patients and 2 of them were in a septic condition on admittance. Two of the Norwegians died of serious infection; 5 were successfully treated with percutaneous drainage in addition to antibiotics and 1 was treated exclusively with antibiotic agents. The clinical history and microorganism associated with psoas abscess seemed to depend on whether or not the patient was an immigrant. Owing to increasing immigration, diagnosis of psoas abscess should be taken into account in Northern countries.