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Crocetin (CCT) is a natural saffron-derived apocarotenoid that possesses healthy properties such as anti-adipogenic, anti-inflammatory, and antioxidant activities. Lipolysis is enhanced in obesity and correlates with a pro-inflammatory, pro-oxidant state. In this context, we aimed to investigate whether CCT affects lipolysis. To evaluate CCT's possible lipolytic effect, 3T3-L1 adipocytes were treated with CCT10µM at day 5 post-differentiation. Glycerol content and antioxidant activity were assessed using colorimetric assays. Gene expression was measured using qRT-PCR to evaluate the effect of CCT on key lipolytic enzymes and on nitric oxide synthase (NOS) expression. Total lipid accumulation was assessed using Oil Red O staining. CCT10µM decreased glycerol release from 3T3-L1 adipocytes and downregulated adipose tissue triglyceride lipase (ATGL) and perilipin-1, but not hormone-sensitive lipase (HSL), suggesting an anti-lipolytic effect. CCT increased catalase (CAT) and superoxide dismutase (SOD) activity, thus showing an antioxidant effect. In addition, CCT exhibited an anti-inflammatory profile, i.e., diminished inducible NOS (NOS2) and resistin expression, while enhanced the expression of adiponectin. CCT10µM also decreased intracellular fat and C/EBPα expression (a transcription factor involved in adipogenesis), thus revealing an anti-adipogenic effect. These findings point to CCT as a promising biocompound for improving lipid mobilisation in obesity.
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OBJECTIVES: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. METHODS: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. RESULTS: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). CONCLUSIONS: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Cirrosis Hepática/epidemiología , ARN/uso terapéutico , España/epidemiologíaRESUMEN
BackgroundRecent and reliable estimates on the prevalence of coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Europe are lacking.AimLeveraged on a study designed to assess HIV/HCV coinfection prevalence, we assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with five similar studies performed since 2002.MethodsThis cross-sectional prevalence study was carried out in 43 centres, and patients were selected using simple random sampling. The reference population comprised 40,322 patients and the sample size were 1,690 patients.ResultsThe prevalence of HIV/HBV coinfection in Spain at the end of 2018 was 3.2%. The prevalence in 2002, 2009, 2015, 2016 and 2017 was 4.9%, 3.4%, 3%, 3.9% and 3%, respectively. Among the HIV/HBV-coinfected patients identified in 2018, 16.7% had cirrhosis according to transient elastography and 26.3% tested positive for antibodies against hepatitis D virus. All HIV/HBV-coinfected patients were receiving drugs with activity against HBV, and 97% of those tested for HBV DNA had an HBV DNA load < 80 IU/mL.ConclusionsThe prevalence of HIV/HBV coinfection in Spain remained stable at around 3% for a decade. Our data could facilitate the design of national programmes to control HBV infection and help identify areas of patient management that need improvement.
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Coinfección , Infecciones por VIH , Hepatitis B , Coinfección/epidemiología , Estudios Transversales , Europa (Continente) , Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Virus de la Hepatitis B , Humanos , Prevalencia , España/epidemiologíaRESUMEN
BACKGROUND: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. METHODS: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. RESULTS: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. CONCLUSIONS: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.
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Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.
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Trazado de Contacto , Ensayos de Liberación de Interferón gamma/normas , Tuberculosis Latente/diagnóstico , Juego de Reactivos para Diagnóstico/normas , Prueba de Tuberculina/normas , Adulto , Análisis Costo-Beneficio , Composición Familiar , Femenino , Humanos , Incidencia , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Servicios Preventivos de Salud/métodosRESUMEN
Background: New direct-acting antiviral agents (DAAs) have shown great efficacy and tolerability in clinical trials and real-life cohorts. However, data are scarce regarding efficacy and safety in cirrhotic HCV/HIV-coinfected patients. Methods: A multicentre prospective analysis was performed in 13 Spanish hospitals, including all cirrhotic HCV/HIV-coinfected patients starting DAA combinations from January to December 2015. Sustained virological response 12 weeks after treatment (SVR12) was analysed. Withdrawal due to toxicity and/or hepatic decompensation and change in liver stiffness measurement (LSM) after HCV treatment were evaluated. Results: Patients (n = 170) were mostly male (n = 125; 74.3%) with the following HCV genotype (Gt) distribution: Gt-1a, 68 (40%); Gt-1b, 21 (12.4%); Gt-4, 47 (27.6%); and Gt-3, 26 (15.3%). Baseline median LSM was 20.6 kPa (IQR 16.1-33.7) and log10 HCV-RNA 6.1 IU/mL (IQR 5.7-6.5). Most patients had a Child-Pugh class A score (n = 127; 74.7%) and 28 (16.5%) had prior hepatic decompensation. There were 89 (52.4%) pretreated patients with 40.4% (n = 36) of null responders. Preferred regimens were as follows: sofosbuvir/ledipasvir + ribavirin, 43 (25.3%) patients; sofosbuvir + simeprevir + ribavirin, 34 (20%); sofosbuvir/ledipasvir, 26 (15.3%) and sofosbuvir + daclatasvir + ribavirin, 25 (14.7%). Overall SVR12 was 92.9% (158/170), without differences between genotypes. Pretreated patients had lower SVR12 rates compared with naive (88.8% versus 97.5%; P = 0.026). Treatment failures were as follows: 7 (4.1%) relapses; 2 (1.2%) lost to follow-up; 1 (0.6%) toxicity-related discontinuation; 1 (0.6%) hepatic decompensation; and 1 (0.6%) viral breakthrough. On-treatment hepatic decompensation was recorded in four (2.4%) patients (encephalopathy and ascites, two each). Paired LSM in 33 patients showed a decrease of 5.6 kPa (95% CI 1.8-9.2; P = 0.004). Conclusions: In our cohort of cirrhotic HCV/HIV-coinfected patients, DAAs were highly safe and efficacious. Viral eradication was associated with a significant decrease in liver stiffness.
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Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/complicaciones , ARN Viral/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Estudios de Cohortes , Coinfección/virología , Quimioterapia Combinada/efectos adversos , Femenino , Fluorenos/administración & dosificación , Fluorenos/efectos adversos , Fluorenos/uso terapéutico , Genotipo , VIH/efectos de los fármacos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Ribavirina/uso terapéutico , Simeprevir/administración & dosificación , Simeprevir/efectos adversos , Simeprevir/uso terapéutico , Sofosbuvir , España/epidemiología , Respuesta Virológica Sostenida , Resultado del Tratamiento , Uridina Monofosfato/administración & dosificación , Uridina Monofosfato/efectos adversos , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapéuticoRESUMEN
BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.
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Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Hepatitis C/epidemiología , Hepatitis C/inmunología , Adolescente , Adulto , Estudios de Cohortes , Coinfección/epidemiología , Coinfección/inmunología , Coinfección/virología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1 , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Carga Viral , Adulto JovenRESUMEN
Hepatitis C virus (HCV) is one of the major causes of chronic hepatitis, cirrhosis, and hepatocellular carcinoma, and the development of HCV-related disease is accelerated in individuals coinfected with human immunodeficiency-1 virus (HIV). In the present study, we correlated different host single-nucleotide polymorphisms (SNPs) in the IL28B, CTLA4, LDLr, and HFE genes and mitochondrial DNA (mtDNA) haplogroups with the outcome of HCV infection and the response to pegylated-interferon plus ribavirin (pegIFN-RBV) treatment. Our study population consisted of 63 Majorcan patients coinfected with HCV and HIV and 59 anonymous unrelated controls. Whereas the population frequency of IL28B alleles was similar to that found in a North-American cohort of European descent, the frequency of the rs12979860 C allele was lower than that determined in other cohorts from Spain. The frequencies of CTLA4 and LDLr polymorphisms were comparable to those reported in other populations. Significant differences between cases and control cohorts occurred only for the H63D mutation of the HFE gene. There were no other differences in the frequencies of other polymorphisms or mtDNA haplogroups. The IL28B rs12979860 CC genotype was shown to be associated with a rapid virological response, and the spontaneous viral clearance rate for HCV was higher in patients with the CTLA4+49 G allele. There was no relationship between SNPs in the LDLr and HFE genes and mtDNA haplogroups and the response to treatment. Our results suggest that the host genetic background plays a significant role in the pegIFN-RBV response of patients coinfected with HCV and HIV.
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Antivirales/uso terapéutico , Coinfección/genética , Infecciones por VIH/genética , Hepacivirus/fisiología , Hepatitis C/genética , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Polimorfismo de Nucleótido Simple , Ribavirina/uso terapéutico , Adulto , Coinfección/tratamiento farmacológico , Coinfección/etnología , Coinfección/virología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/etnología , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , VIH-1/fisiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/etnología , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , España/etnología , Resultado del TratamientoRESUMEN
Chronic hepatitis C virus (HCV) infection is the main cause of advanced and end-stage liver disease world-wide, and an important factor of morbidity and mortality in Human Immunodeficiency virus-1 (HIV-1) co-infected individuals. Whereas the genetic variability of HCV has been studied extensively in monoinfected patients, comprehensive analyses of both patient and virus characteristics are still scarce in HCV/HIV co-infection. In order to find correlates for liver damage, we sought to analyze demographic, epidemiological and clinical features of HCV/HIV co-infected patients along with the genetic makeup of HCV (viral subtypes and lineage studied by nucleotide sequencing and phylogenetic analysis of the NS5B region). We used the Generalized Linear Model (GLM) methodology in order to integrate data from the virus and the infected host to find predictors for liver damage. The degree of liver disease was evaluated indirectly by means of two indexes (APRI and FIB-4) and accounting for the time since infection, to estimate fibrosis progression rates. Our analyses identified a reduced number of variables (both from the virus and the host) implicated in liver damage, which included the stage of HIV infection, levels of gamma-glutamil transferase and cholesterol, and some distinct HCV phylogenetic clades.
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Coinfección/complicaciones , Infecciones por VIH/complicaciones , Hepatitis C Crónica/complicaciones , Interacciones Huésped-Patógeno , Modelos Lineales , Cirrosis Hepática/etiología , Adulto , Femenino , Hepacivirus/genética , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Filogenia , Estudios Retrospectivos , Proteínas no Estructurales Virales/genéticaRESUMEN
BACKGROUND AND AIMS: This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. METHODS: The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. RESULTS: As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (pâ=â0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, pâ=â0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (pâ=â0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (pâ=â0.049 and pâ=â0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (pâ=â0.02 and pâ=â0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, pâ=â0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, pâ=â0.01) remained significant. CONCLUSIONS: In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism.
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Regulación Viral de la Expresión Génica , Variación Genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/genética , Interleucinas/biosíntesis , Farmacogenética/métodos , Proteínas Supresoras de la Señalización de Citocinas/biosíntesis , Adulto , Femenino , Genotipo , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Humanos , Interferón-alfa/metabolismo , Interferones , Masculino , Modelos Genéticos , Modelos Estadísticos , Fenotipo , Polimorfismo Genético , Ribavirina/farmacología , Proteína 3 Supresora de la Señalización de CitocinasAsunto(s)
Neovascularización Patológica/diagnóstico , Vasculitis Retiniana/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Corticoesteroides/uso terapéutico , Antituberculosos/uso terapéutico , Etambutol/uso terapéutico , Humanos , Isoniazida/uso terapéutico , Coagulación con Láser , Masculino , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/etiología , Neovascularización Patológica/cirugía , Pirazinamida/uso terapéutico , Radiografía , Recurrencia , Hemorragia Retiniana/etiología , Vasculitis Retiniana/diagnóstico por imagen , Vasculitis Retiniana/tratamiento farmacológico , Vasculitis Retiniana/etiología , Vasculitis Retiniana/cirugía , Rifampin/uso terapéutico , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/tratamiento farmacológico , Agudeza Visual , Adulto JovenRESUMEN
BACKGROUND: The overall seroprevalence of HTLV infection among pregnant women in Spain is below 0.02% and accordingly universal antenatal screening is not recommended. However, as the number of immigrants has significantly increased during the last decade, this population might warrant specific considerations. OBJECTIVE: To evaluate the seroprevalence of HTLV infection among immigrant pregnant women living in Spain. METHODS: From January 2009 to December 2010 a cross-sectional study was carried out in all foreign pregnant women attended at 14 Spanish clinics. All were tested for HTLV antibodies using a commercial enzyme-immunoassay, being reactive samples confirmed by Western blot or PCR. RESULTS: A total of 3337 foreign pregnant women were examined. Their origin was as follows: Latin America 1579 (47%), North Africa 507 (16%), East Europe 606 (18%), Sub-Saharan Africa 316 (9%), North America and West Europe 116 (3.5%) and Asia and Australia 163 (5%). A total of 7 samples were confirmed as HTLV positive, of which 6 were HTLV-1 and 1 HTLV-2. HTLV-1 infection was found in 5 women coming from Latin America and 1 from Morocco. The only woman with HTLV-2 came from Ghana. The overall HTLV seroprevalence was 0.2%, being 0.3% among Latin Americans and 0.2% among Africans. It was absent among women coming from other regions. CONCLUSIONS: The seroprevalence of HTLV infection among foreign pregnant women in Spain is 0.2%, being all cases found in immigrants from Latin America and Africa. Given the benefit of preventing vertical transmission, antenatal screening should be recommended in pregnant women coming from these regions.
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Infecciones por Deltaretrovirus/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Deltaretrovirus/genética , Infecciones por Deltaretrovirus/virología , Emigrantes e Inmigrantes/estadística & datos numéricos , Femenino , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Seroepidemiológicos , España/epidemiología , España/etnología , Adulto JovenRESUMEN
BACKGROUND: Although paradoxical virological and immunological response after HAART has been well studied, intestinal lymphangiectasia (IL) in HIV-1 infected patients has not previously described. METHODS: To describe HIV patients who developed IL. DESIGN: Clinical Case series. PATIENTS: 4 patients with HIV and IL diagnosis based on clinical, endoscopic and pathological findings. RESULTS: All four cases had prior mycobacterial infections with abdominal lymph node involvement and a very low CD4 cell count nadir. They developed intestinal lymphangiectasia despite appropriate virological suppression with HAART and repeatedly negative mycobacterial cultures. Two patients were clinically symptomatic with oedemas, ascites, diarrhoea, asthenia, weight loss; but the other two were diagnosed with malabsorption as a result of laboratory findings, with hypoproteinemia and hypoalbuminemia. Three of them were diagnosed by video capsule endoscopy. CONCLUSIONS: IL should be considered in HIV-1 infected patients who present with clinical or biochemical malabsorption parameters when there is no immunological recovery while on HAART.
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Infecciones por VIH/complicaciones , VIH-1 , Linfangiectasia Intestinal/complicaciones , Síndromes de Malabsorción/etiología , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Endoscopía Capsular , Resultado Fatal , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Humanos , Hipoproteinemia/etiología , Linfangiectasia Intestinal/diagnóstico , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Tuberculosis Miliar/complicacionesRESUMEN
Hepatitis C virus (HCV) infection is the most important cause of chronic hepatitis, cirrhosis and end-stage liver disease leading to liver transplantation worldwide. Chronic infection by HCV causes liver fibrosis, which is accelerated by unknown mechanisms in patients with human immunodeficiency virus-1 (HIV-1) coinfection. Although the genetic variability of both HCV and HIV has been extensively studied in the context of monoinfections, more limited data is available regarding HCV-HIV coinfection. HCV disease progression among HIV coinfected patients may be influenced not only by demographic, epidemiological and clinical background variables, but also by genetic differences in infecting viruses. To explore this issue, we carried out a study in coinfected patients trying to associate the degree of liver damage to several demographic, clinical, and epidemiological characteristics of the patients, and also to the genetic variability of HCV between patients. For this purpose, we have applied different statistical techniques including the statistical generalized linear model (GLM) framework. The stage of fibrosis was indirectly measured by noninvasive means using the indexes Forns, APRI and FIB-4. HCV genetic variability between patients was estimated by sequencing the core region and by reconstructions of consensus maximum parsimony phylogenetic trees with 50% and 75% bootstrap majority rules. The results showed a direct correlation of the fibrosis biomarkers with the AST/ALT ratio, MoftIDU and with 3a HCV genotype clades, among others.
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Infecciones por VIH/complicaciones , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Cirrosis Hepática/virología , Polimorfismo Genético , Secuencia de Bases , Progresión de la Enfermedad , Variación Genética , Infecciones por VIH/epidemiología , VIH-1 , Haplotipos , Hepatitis C Crónica/epidemiología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Pruebas de Función Hepática , Filogenia , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , ARN ViralRESUMEN
UNLABELLED: Although two pegylated interferons (Peg-IFN) are available to treat chronic hepatitis C virus (HCV) infection, no head-to-head comparative studies have been published. We aim to compare the efficacy and safety of PEG IFN alfa-2b (PEG 2b) versus PEG IFN alfa-2a (PEG 2a), plus ribavirin (RBV). A prospective, randomized, multi-center, open-label clinical trial including 182 human immunodeficiency virus (HIV)-hepatitis C virus (HCV) patients naïve for HCV therapy was performed. Patients were assigned to PEG 2b (80-150 mug/week; n = 96) or PEG 2a (180 mug/week; n = 86), plus RBV (800-1200 mg/day) for 48 weeks. The primary endpoint was sustained virological response (SVR: negative HCV-RNA 24 weeks after completion of treatment). At baseline, both groups were well balanced: 73% male; 63% HCV genotype 1 or [corrected] 4; 29% had fibrosis index of 3 or greater. The overall SVR was 44% (42% PEG 2b versus 46% PEG 2a, P = 0.65). Among genotypes 1 or [corrected] 4, SVRs were 28% versus 32% (P = 0.67) and 62% versus 71% (P = 0.6) in genotypes 2 or [corrected] 3 for PEG 2b and PEG 2a, respectively. Early virological response (EVR; >or=2 log reduction from baseline or negative HCV-RNA at week 12) was 70% in the PEG 2b group and 80% in the PEG 2a group (P = 0.13), reaching a positive predictive value of SVR of 64% and a negative predictive value of 100% in both arms. Side effects were present in 96% of patients but led to treatment discontinuation in 10% of patients (8% on PEG 2b and 13% on PEG 2a, P = 0.47). CONCLUSION: In patients with HIV, HCV therapy with PEG 2b or PEG 2a plus RBV had no significant differences in efficacy and safety.
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Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , Hepatitis C Crónica/etiología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Proteínas RecombinantesRESUMEN
BACKGROUND: The combination of pegylated interferon (PEG-IFN) plus ribavirin (RBV) is the standard of care for hepatitis C virus (HCV) treatment in HIV-coinfected individuals. In 2007, abacavir (ABC)-based antiretroviral therapy was, for the first time, reported to be associated with early virological failure during HCV treatment. The aim of our study was to evaluate the effect of ABC on the response rate to HCV therapy. METHODS: A retrospective analysis of HIV-HCV-coinfected patients treated with PEG-IFN and weight-adjusted RBV in four hospitals in Spain was performed. An analysis of baseline descriptive variables was conducted. Logistic regression models were used to test possible associations between non-response and pretreatment characteristics, including antiretroviral drugs. RESULTS: A total of 244 HIV-HCV-coinfected patients treated with PEG-IFN and RBV were included. Overall, 85% of patients were on highly active antiretroviral therapy; of these patients, 24% received ABC-based regimens. The most frequent genotypes were 1 and 3. RBV dosing was 213.2 mg/kg/day in 97% of the patients. In the global intent-to-treat analyses, 46.3% of patients reached a sustained virological response (SVR; 46.2% in ABC group versus 46.7% in non-ABC group, P=1). The only two factors in the multivariate analysis that were statistically associated with an increased risk of failure to achieve SVR were HCV genotypes 1 or 4 and older age. The use of ABC was not associated with failure to achieve SVR at any of the other time points evaluated. CONCLUSIONS: Our data suggest that the use of ABC-based regimens in the context of HCV therapy does not negatively affect the outcome of this treatment.
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Fármacos Anti-VIH/uso terapéutico , Antivirales/uso terapéutico , Didesoxinucleósidos/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Fármacos Anti-VIH/administración & dosificación , Antivirales/administración & dosificación , Didesoxinucleósidos/administración & dosificación , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/uso terapéutico , Masculino , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: There is little information on bacteremia in very elderly patients. This study describes the characteristics of bacteremia in this population. METHODS: This is a prospective study investigating bacteremia episodes in patients over 80 years old in comparison with episodes in patients aged 18-64 and 65-79 years. RESULTS: A total of 146 bacteremia episodes were analyzed in patients over 80 years old. Comorbidity was documented in 66.4% and immunodeficiency in 6.8% of patients. Among the total, 82.2% had no underlying disease or a disease considered non-fatal. Eighty episodes were community-acquired. The main infectious foci included primary (25.3%) and urinary tract (20.5%) infection, and the most frequent isolates were Escherichia coli (28.2%), coagulase-negative Staphylococcus (14.7%) and S. aureus (13.6%). Sepsis or septic shock occurred in 55.5% of the cases, and 31 patients died due to a bacteremia-related cause. Immunodeficiency was less frequent in patients over 80 years old, but they had a higher proportion of community-acquired infections and gram-negative infections. Bacteremia-related mortality was highest in the oldest group of patients and was associated with a fatal or ultimately fatal underlying disease, S. aureus infection, and inappropriate empirical antibiotic treatment. A lower Pitt severity score was related to lower mortality risk. CONCLUSIONS: Very elderly bacteremic patients showed a lower frequency of immunodeficiency, a higher percentage of community-acquired and gram-negative infections. Bacteremia-related mortality was greater in the most elderly group and was associated with fatal or ultimately fatal underlying disease, S. aureus infection and initiation of inappropriate empirical antibiotic treatment.
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Anciano de 80 o más Años , Bacteriemia/epidemiología , Adolescente , Adulto , Edad de Inicio , Anciano , Bacteriemia/inmunología , Bacteriemia/mortalidad , Infecciones Comunitarias Adquiridas/epidemiología , Susceptibilidad a Enfermedades , Femenino , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/inmunología , Mortalidad Hospitalaria , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Choque Séptico/epidemiología , Choque Séptico/inmunología , España/epidemiología , Infecciones Urinarias/epidemiologíaRESUMEN
BACKGROUND: The combination of indinavir, a protease inhibitor, and reverse-transcriptase inhibitors is widely used in the treatment of HIV-1 infection. However, precipitation of indinavir crystals in the renal tubular lumen due to the drug's aqueous insolubility may result in characteristic symptoms of flank pain or classic renal colic. An in vitro study has shown that addition of escin to synthetic urine containing indinavir delayed the crystallization time of indinavir. OBJECTIVE: This study examined the efficacy and tolerability of the addition of escin to highly active antiretroviral therapy containing indinavir to delay the crystallization time of indinavir in urine. METHODS: This was a multicenter, randomized, open-label, controlled, 4-period crossover trial in which each period lasted 4 weeks. HIV-1-infected adults receiving treatment with indinavir plus 2 nucleoside analogue reverse-transcriptase inhibitors in whom plasma viral loads had been undetectable (HIV-1 RNA <200 copies/mL) for at least 6 months were randomly assigned to 1 of 2 groups based on the timing of the initiation of escin. Group I received escin during the second and third treatment periods, and group II received escin during the first and fourth treatment periods. The primary end point was the in vitro crystallization time of indinavir in 24-hour urine specimens, determined at the end of each 4-week period. Tolerability was assessed based on the number of patients with a rebound in plasma viral load and on the numbers of clinically and biologically relevant adverse events (including those requiring discontinuation of treatment). Clinical and laboratory evaluations were performed throughout each 4-week period. RESULTS: Fifty HIV-1-infected patients were enrolled, 47 were randomized to treatment (40 [85.1%] men, 7 [14.9%] women; median [interquartile range] age, 36 [34-45] years), and 30 completed the study. Urine pH and plasma and urine indinavir concentrations were unaffected by the addition of escin to antiretroviral treatment. The mean time to the onset of crystallization was 14.7 minutes with escin (95% Cl, 11.8-17.5) and 9.9 minutes without it (95% Cl, 6.7-13.1). Therefore, the addition of escin increased the mean crystallization time by 5.5 minutes (95% Cl, 1.5-9.5; P = 0.008), representing the overall capacity of study treatment to inhibit indinavir crystallization in the urine. Three of 47 patients had mild gastrointestinal symptoms associated with escin treatment. No episodes of nephrolithiasis were recorded during the study or after the completion of study treatment. CONCLUSION: The results of this prospective clinical trial of the effect of escin on indinavir crystallization time support the possibility that indinavir-associated nephrolithiasis may be prevented by means other than overhydration. Further research is needed in greater numbers of patients over longer follow-up times.