Cytokine profile levels and their relationship with parasitemia and cardiomyopathy in people with Chagas disease in Spain. A prospective observational study.

Immunoregulatory networks may have a role in controlling parasitemia in the chronic phase of human Chagas disease. The aim was to describe the serum cytokine profile of Trypanosoma cruzi in chronically infected patients and to evaluate its relationship with parasitemia and Chagas cardiomyopathy.This prospective observational study included adult patients with chronic Chagas disease. Demographic and clinical data were collected, and peripheral blood samples were used to perform T. cruzi real-time polymerase chain reaction (RT-PCR) and determine the serum cytokine profile.Fifty-eight patients were included; 17 (29.3%) had positive RT-PCR results. This group had a higher median concentration of TNF-α (p = 0.003), IL-6 (p = 0.021), IL-4 (p = 0.031), IL-1ß (p = 0.036), and IL-17A (p = 0.043) than those with a negative RT-PCR. Patients with cardiac involvement had a higher median concentration of IL-5 (p = 0.016) than those without.These results reinforce the key role that cytokines play in Chagas disease patients with parasitemia and cardiac involvement.

Chagas disease screening in pregnant Latin American women: Adherence to a systematic screening protocol in a non-endemic country.

BACKGROUND: Chagas disease (CD) is a chronic parasitic disease caused by Trypanosoma cruzi and is endemic to continental Latin America. In Spain, the main transmission route is congenital. We aimed to assess adherence to regional recommendations of universal screening for CD during pregnancy in Latin American women in the province of Alicante from 2014 to 2018. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective quality study using two data sources: 1) delivery records of Latin American women that gave birth in the 10 public hospitals of Alicante between January 2014 and December 2018; and 2) records of Chagas serologies carried out in those centers between May 2013 and December 2018. There were 3026 deliveries in Latin American women during the study period; 1178 (38.9%) underwent CD serology. Screening adherence ranged from 17.2% to 59.3% in the different health departments and was higher in Bolivian women (48.3%). Twenty-six deliveries (2.2%) had a positive screening; CD was confirmed in 23 (2%) deliveries of 21 women. Bolivians had the highest seroprevalence (21/112; 18.7%), followed by Colombians (1/333; 0.3%) and Ecuadorians (1/348; 0.3%). Of 21 CD-positive women (19 Bolivians, 1 Colombian, 1 Ecuadorian), infection was already known in 12 (57.1%), and 9 (42.9%) had already been treated. Only 1 of the 12 untreated women (8.3%) was treated postpartum. Follow-up started in 20 of the 23 (87.0%) neonates but was completed only in 11 (47.8%); no cases of congenital transmission were detected. Among the 1848 unscreened deliveries, we estimate 43 undiagnosed cases of CD and 1 to 2 undetected cases of congenital transmission. CONCLUSIONS/SIGNIFICANCE: Adherence to recommendations of systematic screening for CD in Latin American pregnant women in Alicante can be improved. Strategies to strengthen treatment of postpartum women and monitoring of exposed newborns are needed. Currently, there may be undetected cases of congenital transmission in our province.

Condición clínica y niveles de colinesterasa de trabajadores informales dedicados a la fumigación con plaguicidas / Clinical condition and colinesterase levels of informal workers dedicated to fumigation with pesticides

Resumen Introducción. Las prolongadas exposiciones a diversos plaguicidas pueden alterar la salud de los individuos mediante alteración de la funcionalidad de la enzima colinestera. Objetivo. Determinar los síntomas clínicos por efectos probables de inhibición de las enzimas colinesterasas en un grupo de fumigadores del sector informal de la economía. Materiales y métodos. Diseño analítico, prospectivo. A cada uno de los 256 fumigadores sin otras condiciones susceptibles de afectar la enzima, se le tomó semestralmente muestra de 10 mL de sangre venosa periférica; hasta completar 4 mediciones. Cada muestra de sangre fue repartida en dos tubos heparinizados, preservados en frío (2-8°C) hasta 10 horas máximo. El rango de normalidad utilizado como referencia fueron las cifras encontradas para Colombia por Carmona-Fonseca en adultos no expuestos utilizando la técnica EQM®, la misma que ha sido utilizada en este estudio. Resultados. La edad de inicio en la tarea de fumigación fue de 14 a 16 años (73%), 100% se mantuvo laboralmente activos, en contacto laboral con insecticidas órgano-fosforados y diversos compuestos activos herbicidas durante tiempo de exposición entre 8 y 28 años (67%). El promedio de las cuatro mediciones de colinesterasa eritrocitaria en fumigadores osciló entre 33.8 y 27.6, con descensos progresivos del valor inicial (67%) en las mediciones sucesivas, existe 37.2% de sintomáticos para intoxicación crónica. Conclusiones. La exposición continuada a plaguicidas refleja alteraciones de la colinesterasa eritrocitaria entre los fumigadores informales. Discusión. Hallazgos similares con Abou-Hatab en relación con resultados y la edad, entre expuestos sintomáticos se evidencia intoxicación crónica.

Abstract Introduction. Prolonged exposures to various pesticides can alter the health of individuals by altering the functionality of the cholinesterase enzyme. Objective. To determine the clinical symptoms by probable effects of inhibition of the cholinesterase enzymes in a group of fumigators of the informal sector of the economy. Materials and methods. Analytical, prospective design. To each of the 256 fumigators without other conditions susceptible to affect the enzyme, a 10mL sample of peripheral venous blood was taken every six months; until completing 4 measurements. Aach blood sample was divided into two heparinized tubes, preserved in cold (2-8°C) up to 10 hours-maximum. The normality range used as a reference was the figures found for Colombia by Carmona-Fonseca in adults not exposed using the EQM® technique, the same one that has been used in this study. Results. The age of initiation in the fumigation was 14 to 16 years (73%), 100% remained labor-active, in labor contact with organophosphorus insecticides and various herbicidal active compounds during exposure time between 8 and 28 years (67%). The average of the four measurements of erythrocyte cholinesterase in sprayers ranged between 33.8 and 27.6, with progressive decreases of the initial value (67%) in the successive measurements; there are 37.2% of symptomatic for chronic intoxication. Conclusions. The continuous exposure to pesticides reflects alterations in the erythrocyte cholinesterase among the informal fumigators. Discussion. Similar findings with Abou-Hatab in relation to results and age, among symptomatic exposed chronic poisoning are evidenced.

Interferon-free therapy for treating hepatitis C virus in difficult-to-treat HIV-coinfected patients.

BACKGROUND/AIMS: Data regarding the use of all-oral direct-acting antivirals in HIV/hepatitis C virus (HCV)-coinfected patients with advanced liver fibrosis are required, because they are generally under-represented in clinical trials. This study sought to evaluate the use of these drugs in a cohort of coinfected patients, mostly with factors that have previously been recognized as predictors of treatment failure. METHODS: COINFECOVA-2 is an observational, multicenter study conducted in Eastern Spain. Data of all HIV/HCV-coinfected patients treated with direct-acting antiviral under real-life conditions were retrospectively collected, and factors associated with treatment success or safety were analysed. RESULTS: Among 515 included patients, 96% were on antiretroviral therapy and 89.5% had an HIV-RNA less than 50 copies/ml. HCV genotype (G) distribution was 47% G-1a, 20% G-4, 14.4% G-1b, and 12.8% G-3. Patients with cirrhosis were 54.2%, and 46% failed to prior HCV-therapies. Overall, 92.8% patients (95% confidence interval: 90.2-94.9) achieved sustained virologic response (SVR12). Cirrhosis was the only factor associated with treatment failure, and SVR12 rate was significantly lower in patients with liver stiffness at least 21 kPa. Adverse events were reported in 36.7%, but only two patients (0.4%) discontinued treatment because of adverse events. The bivariate analysis showed an association between ribavirin use and an increased risk of adverse events (odds ratio 2.84; 95% confidence interval: 1.95-4.1; P ≤ 0.0001). CONCLUSION: This heterogeneous cohort of coinfected patients showed a high rate of SVR12. Among cirrhotic patients, those with a liver stiffness at least 21 kPa had a higher probability of treatment failure. Ribavirin use seems to increase the appearance of adverse events.

Delirio de pacientes con síndrome coronario agudo en una unidad de cuidados intensivos / Delirium in patients with acute coronary syndrome in an intensive care unit

Introducción: el delirio es una variación aguda del estado de conciencia, frecuente en unidad de cuidado intensivo (UCI). Su incidencia varía, presentando diferentes características clínicas correlacionadas. Objetivo: determinar la incidencia de delirio en pacientes con Síndrome Coronario Agudo (SCA) en una UCI, las características clínicas asociadas, y su correlación con el grado de severidad de la enfermedad. Material y métodos: estudio descriptivo, pros-pectivo, cuantitativo. Se aplicó herramienta diagnóstica CAM-ICU, a 24 pacientes para detectar la presencia de delirio en casos de síndrome coronario. Resultados: la incidencia de delirio estimada fue de 4 casos por cada 1000 de Síndrome Coronario Agudo; la edad promedio para pacientes con delirio fue 67 años. El valor de Cramérs V obtenido de 0.589 sugiere una moderada relación entre "X" (la situación clínica medida con Apache II) y "Y" (la presencia de delirio identificada con CAM-ICU); al igual que la relación entre el delirium y la evaluación objetiva de la gravedad utilizando la escala APACHE-II (Phi 283). Conclusión: el delirio fue una manifestación neu-rológica de baja incidencia entre los pacientes con SCA internados en UCI; el coeficiente de Cramérs V obtenido indico intensidad moderada en la asociación estadística entre delirium y severidad del cuadro clínico.

Dual therapy with darunavir/r plus etravirine is safe and effective as switching therapy in antiretroviral experienced HIV-patients. The BITER Study.

INTRODUCTION: Switching therapy studies are usually designed as second-line antiretroviral treatment (ART) in patients without previous virologic failures. Combined ART (cART) with DRV/r and ETR has a good pharmacokinetic profile, high genetic barrier and has been proved as rescue therapy. The aim of our study was to analyze efficacy and safety of therapy with DRV/r plus ETR in treatment experienced HIV-patients with previous therapeutic failures that need to switch ART. We present results at first 24 weeks. METHODS: Multicentre retrospective observational study. INCLUSION CRITERIA: adult HIV-patients on ART with HIV-VL <1000 cop/mL who started their ART with DRV/r (600/100 bid or 800/100 qd)+ETR by adverse events, non-adherence, tolerability or prevention of future complications. Patients with acute AIDS events, HBV, pregnancy, drug addiction or previous selected mutations to DRV or ETR were excluded. RESULTS: Ninety-nine patients were included, mean age: 47 years (r: 22-79); 70% men, 40.4% previous AIDS event and 39.3% HCV. Ninety-one patients had received ≥3 cART regimens and 45≥5, 75 patients had HIV-VL <50 cop/mL and 24 low-level viremia (LLV): 297.5±261.4 cop/mL, CD4+ 568±279 cells/µL. ART before switching: NRTI+PI/r (33%), NNRTI (17%), PI/r+NNRTI (23%), PI/r+INI (13%), other (14%). Main reason to switching was: toxicity/intolerance 50 patients (renal 32%, gastrointestinal: 14%, hyperlipidaemia 10%; osteopenia/osteoporosis: 6%); improving adherence 26 patients; prevention of complications 19 patients. Nine subjects withdrew ART during follow-up because: intolerance or new toxicity three; non-adherence two; simplification to DRV/r monotherapy two; persistence of previous toxicity one; virologic failure one. At week 24, among patients who continued with DRV/r+ETR (n=90): 81 (89%) had VL<50 cop/mL, in those with with HIV-VL<50 at baseline (67/90), 94% persisted with <50 cop., and in those with LLV (24/90), 61% (n=14) achieved a VL<50 cop. We didn't observe any significant difference in lab parameters between baseline and week 24. Estimated glomerular filtrate rate increased from 83.4±24.7 to 88.5±56.8 mL/min, p=NS. Regarding reason to switching, it improved in 42 cases, no changes: 20 cases; worsened: 4 cases, and non-applicable or unknown: 24 cases. CONCLUSIONS: Switching to dual therapy with DRV/r+ETR is an effective strategy in selected heavily experienced ART patients, even in those with LLV (<1000 cop/mL). This cART is safe and well tolerated, can reduce number of pills and improve adherence.

Telaprevir or boceprevir in HIV/HCV-1 co-infected patients in a real-life setting. Interim analysis (24 weeks). COINFECOVA-SEICV study.

INTRODUCTION: In general, HIV co-infected patients included in clinical trials evaluating the hepatitis C virus (HCV) therapy with telaprevir (TVR) or boceprevir (BOC) with advanced fibrosis, are scarce. We analyze data concerning the use of these drugs in a real-life clinical setting with patients affected by a more advanced degree of fibrosis in a Spanish cohort. METHODS: We evaluated safety and efficacy in an interim analysis encompassing the first 24 weeks of triple therapy with peginterferon (alfa-2a or alfa-2b), ribavirin and TVR or BOC in an observational, multicentre study. HIV/HCV genotype 1 co-infected patients beginning therapy from January 2012 to July 2013 were included. RESULTS: Enrolled patients were 155 (144 patients on TVR and 11 on BOC), average age was 47 years, 83% were male. With respect to HCV treatment, 44% were naïve, 13% relapsers, 17% partial responders, 21% null responders, and in seven patients, the previous response was unknown. All but three (98%) were under antiretroviral therapy (ART) (other than reverse transcriptase inhibitors, the backbone was raltegravir 43%, atazanavir 35%, and etravirine 28%). Median HCV-RNA at baseline was 6.1 log10, 54% were cirrhotic and 38% F3. At week 4, 93% of patients continued on therapy, 81% at w12, and 73% at w24. Virological failure was observed more frequently in: cirrhotic patients (19% [95% CI, 11-27]) vs F3 (12% [CI, 4-20]); patients with TT allele of the IL28B polymorphism (40% [CI, 18-61]) vs CT (21% [CI, 12-31]), or CC (2,2% [CI, -2-6]); previous null responders (37.5% [CI, 21-54]) vs partial responders (15.4% [CI, 1-29]), naïve (13% [CI, 5-21]) or relapsers (0% [CI, 0-0]); and in patients with a genotype subtype 1a (23.6% [CI, 57-76]) vs 1b (8.1% [CI, -1-17]). Overall, 17% had virological failure and in 8% treatment was discontinued due to adverse events. Severe adverse events occurred in 30 patients (19%). Haematologic disorders were the most common type including severe anaemia in 12 (7.7%) patients. Erythropoietin was employed in 41 patients (26.4%) and 11 (7.1%) received blood transfusions. Nineteen patients (12.2%) were treated with G-CSF, and 17 (11%) with thrombopoietin-receptor agonists. Five patients died (3.2%), three due to hepatic decompensation, one due to pneumonia and one due to pulmonary hypertension. CONCLUSIONS: In a real-life setting, therapy against HCV in co-infected patients with advanced liver fibrosis shows high virologic success at 24 weeks. However, frequent haematologic disorders are observed and a close monitoring and an intensive therapy are needed to optimize the results.

Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain.

BACKGROUND: To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. METHODS: All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. RESULTS: Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. CONCLUSIONS: HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.

Multicenter epidemiological and clinical study on imported Chagas diseases in Alicante, Spain.

Recently, there has been an increase in the number of patients with Chagas disease outside of areas that are generally considered endemic. The aim of this investigation is to describe the clinical profile of a series of patients with Chagas disease in Alicante, Spain, which is a province located on the coast of the Mediterranean Sea. This study was performed at four general hospitals in Alicante between January 2002 and May 2011. A total of 128 patients from seven countries were diagnosed with Trypanosoma cruzi. The main country of origin of these patients was Bolivia (n5101; 78.9%), and the median of age of these patients was 35 years (range: 0­72 years). Four (3.3%) patients were children under 14 years of age, and 81 (63.3%) were female. Polymerase chain reaction (PCR) was used to analyze 106 patients, 66.0% of whom demonstrated positive PCR results. Visceral involvement was diagnosed in 26.8%: 24.1% demonstrated cardiac involvement, 0.9% demonstrated gastrointestinal involvement, 0.9% demonstrated cardiac and gastrointestinal involvement, and 0.9% demonstrated involvement of the central nervous system. Syncope was found to be associated with cardiomyopathy (28.0% versus 5.2%) (odds ratio: 6.5; 95% confidence interval: 1.5­27.1). Seventy-six patients received treatment with benznidazole, of whom 57 (75.0%) completed the treatment course without significant adverse events and 17.1% discontinued benznidazole due to adverse events. In total, 50% of patients experienced documented adverse reactions. Among patients with positive PCR results before treatment, all demonstrated negative PCR results following treatment. In conclusion, majority of our patients were female Bolivians immigrants, one of four of our patients demonstrated cardiac involvement, and treatment tolerance was poor. It is important to improve the clinical and epidemiological knowledge of Chagas disease in nonendemic with additional multicenter studies in order to determine the magnitude of this problem and provide improved public health and health resource planning.

Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations.

We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase-inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment-naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release) that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment-naïve patients, and TRANxITION, a study carried out in antiretroviral treatment-experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.

Cross-sectional epidemiology of hepatitis C virus detection and treatment in HIV-infected patients.

BACKGROUND: Sustained virologic response to peginterferon plus ribavirin reduces liver-related complications and mortality in patients co-infected with HIV and hepatitis C virus. Therefore, the presence of any barriers to start hepatitis C virus therapy should be identified and eliminated in order to recruit all eligible patients. METHODS: Cross-sectional study. In a HIV referral clinic we assessed the proportion of patients eligible for hepatitis C virus evaluation and treatment according to consensus guidelines. RESULTS: We identified 134 patients with hepatitis C virus and HIV co-infection. Twenty-one patients were excluded from the analysis due to never attending the HIV clinic (n=12) or having hepatitis C virus RNA not detectable (n=9). In the remaining 113 patients, only 61% had identification of hepatitis C virus genotype and quantification of hepatitis C viral load. Thirty-six patients started peginterferon plus ribavirin, and 16 (44%) achieved sustained virologic response. Seventy-seven patients did not receive treatment for hepatitis C virus due to the presence of medical contraindications (n=22), provider barriers (n=15), or patient barriers (n=40). Multivariate analysis identified lower education degree (odds ratio: 4.53; 95% confidence intervals: 1.36-15.16, p=0.014) and patient civil status single, separated or widower (odds ratio: 4.81; 95% confidence intervals: 1.54-14.99, p=0.007) as the independent determinants associated to not initiating therapy for hepatitis C virus infection in patients with barriers. CONCLUSION: A minor proportion of HIV-infected patients received appropriate assessment and treatment for hepatitis C virus infection. Social disadvantages require multidisciplinary models of health care to improve hepatitis C virus treatment initiation and success.

Epidemiology of urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli.

OBJECTIVES: To describe the epidemiology of urinary tract infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. METHODS: We performed three studies: a trend study (1999 to 2004) to assess the evolution and origin of ESBL-producing E. coli isolates from urine samples; a comparison of the susceptibility patterns of ESBL-producing E. coli and a random sample of non-ESBL-producing E. coli isolated in the same interval, and a retrospective chart review to determine the risk factors for acquisition of, and outcomes from, urinary tract infections caused by ESBL-producing E. coli (n = 61) compared with a random sample of non-ESBL-producing E. coli urinary tract infections (n = 61) from patients attending our institution and matched by temporal occurrence. RESULTS: ESBL-producing E. coli significantly increased from 2 (0.20%) to 89 (5.52%) isolates per year (P value for trend = 0.000). Of the 161 patients with urinary tract infections caused by ESBL-producing E. coli, 100 (62%) were attending ambulatory health centers, and 61 (38%) were attending the hospital. ESBL-producing E. coli showed a significant reduction in the susceptibility to most antimicrobials, although carbapenems and fosfomycin retained significant activity. The chart review study showed that previous treatment with fluoroquinolones (odds ratio 12.98, 95% confidence interval 1.81 to 106.51, P = 0.017) and the presence of a urinary catheter (odds ratio 2.64, 95% confidence interval 1.01 to 6.88, P = 0.047) were independent risk factors associated with infections caused by ESBL-producing E. coli. CONCLUSIONS: ESBL-producing E. coli is a problem of increasing importance. Our study results may help physicians select appropriate antimicrobial therapy in patients suspected of having urinary tract infections caused by ESBL-producing E. coli.

Net benefits of resistance testing directed therapy compared with standard of care in HIV-infected patients with virological failure: A meta-analysis.

BACKGROUND: We incorporated the latest available information to evaluate the net benefit of using resistance testing in HIV-infected patients with virological failure. METHODS: Meta-analysis of randomized controlled trials comparing the clinical impact of selecting antiretroviral therapy according to results of resistance testing (phenotype or genotype) or according to the standard of care. The population studied included HIV-infected patients with virological failure. The outcome measures were the proportion of patients with HIV-RNA below the detection limit, and the decline in HIV-RNA and increase in CD4 lymphocyte count at the end of follow-up (< or = 24 weeks). Clinical trials were identified through searches in MEDLINE, EMBASE and proceedings from major infectious diseases meetings. RESULTS: Eight trials including a total of 1810 patients were eligible. Therapy guided by resistance testing resulted in a higher percentage of patients with HIV-1 RNA below the detection limit at the end of follow-up (< or = 24 weeks) as compared with the standard of care (40.2% vs. 32.9%). The pooled risk ratio was 1.23; 95% CI 1.09-1.40, p = 0.0009; test for heterogeneity I(2)=0%; p = 0.46). The number needed to treat [NNT] was 13 (95% CI: 9-25). Subgroup analysis showed greater benefits in therapy guided by genotype testing with expert interpretation, when compared with standard of care (NNT: 5; 95% CI: 3-9; p = 0.06). The heterogeneity among trials for evaluating HIV-1 RNA decline and CD4 lymphocyte cell count increase made unfeasible pooling the results across studies. CONCLUSION: Genotype testing with expert interpretation showed the greatest benefit for guiding therapy in patients with HIV infection and virological failure.

Net benefits of resistance testing directed therapy compared with standard of care in HIV-infected patients with virological failure: A meta-analysis

Antecedentes. Hemos incorporado la información más reciente para evaluar el beneficio obtenido tras realizar pruebas de resistencia en pacientes con infección por virus de la inmunodeficiencia humana (VIH) y fracaso virológico. Métodos. Metaanálisis de ensayos clínicos aleatorizados que comparaban el impacto clínico de los cambios de tratamiento antirretroviral dirigidos según el test de resistencia (fenotipo o genotipo) o según las recomendaciones estándar. La población estudiada fue los pacientes con infección por VIH y fracaso virológico. Las medidas de desenlace analizadas fueron: la proporción de pacientes con ARN-VIH no detectable, descenso de ARN-VIH e incremento de linfocitos CD4 al final del seguimiento. Los ensayos clínicos fueron identificados en búsquedas realizadas en Medline, Embase y libros de congresos. Resultados. Identificamos 8 ensayos clínicos y un total de 1.810 pacientes. El tratamiento guiado por tests de resistencia incrementó la proporción de pacientes con ARN-VIH no detectable (40,2% frente a 32,9%) al final del seguimiento (<= 24 semanas). El riesgo relativo combinado fue 1,23 (intervalo de confianza del 95% [IC 95%]: 1,09 a 1,41; p = 0,0009); no hubo heterogeneidad entre los estudios (I 2 5 0%; p = 0,46). El número de pacientes necesario a tratar (NNT) fue de 13 (8 a 27). El análisis de subgrupos identificó un mayor beneficio cuando se utilizaron tests de resistencia genotípicos interpretados por expertos (NNT: 5; IC 95%: 3 a 9; p = 0,06). Hubo heterogeneidad significativa entre los estudios al evaluar la reducción de ARN-VIH y el incremento de linfocitos CD4, ello impidió combinar los resultados. Conclusión. En pacientes con infección por VIH y fracaso virológico el mayor beneficio correspondió al tratamiento guiado por los tests genotípicos de resistencia interpretados por expertos (AU)

Background. We incorporated the latest available information to evaluate the net benefit of using resistance testing in HIV-infected patients with virological failure. Methods. Meta-analysis of randomized controlled trials comparing the clinical impact of selecting antiretroviral therapy according to results of resistance testing (phenotype or genotype) or according to the standard of care. The population studied included HIV-infected patients with virological failure. The outcome measures were the proportion of patients with HIV-RNA below the detection limit, and the decline in HIV-RNA and increase in CD4 lymphocyte count at the end of follow-up (<= 24 weeks). Clinical trials were identified through searches in MEDLINE, EMBASE and proceedings from major infectious diseases meetings. Results. Eight trials including a total of 1810 patients were eligible. Therapy guided by resistance testing resulted in a higher percentage of patients with HIV-1 RNA below the detection limit at the end of follow-up (<= 24 weeks) as compared with the standard of care (40.2% vs. 32.9%). The pooled risk ratio was 1.23; 95% CI 1.09-1.40, p = 0.0009; test for heterogeneity I 2 5 0%; p = 0.46). The number needed to treat [NNT] was 13 (95% CI: 9-25). Subgroup analysis showed greater benefits in therapy guided by genotype testing with expert interpretation, when compared with standard of care (NNT: 5; 95% CI: 3-9; p = 0.06). The heterogeneity among trials for evaluating HIV-1 RNA decline and CD4 lymphocyte cell count increase made unfeasible pooling the results across studies. Conclusion. Genotype testing with expert interpretation showed the greatest benefit for guiding therapy in patients with HIV infection and virological failure (AU)

[Interruption of antiretroviral therapy in chronically HIV-infected patients]. / Interrupción del tratamiento antirretroviral en pacientes con infección crónica por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: To describe the immunological, virological and clinical outcomes of HIV-infected patients who stop antiretroviral therapy (ART) and to identify the factors related to durability. PATIENTS AND METHOD: Retrospective study of patients who interrupt therapy after six months without clinical events, level of CD4+ > or = 500 cells/microl and HIV RNA > or = 5,000 copies/ml (3.7 log10). RESULTS: In October 2004, 44 patients were included, 32 (72%) of them were stables after one year of ART cessation (group A) and 12 (28%) patients had to restart therapy due to a decreased CD4+ count < 300 cells/microl (group B). Both groups were compared. CD4 cell count nadir (414 cells/microl [199] versus 171 cells/microl [107]; p = 0.000) and CD4+ count level at time of ART stop (920 [302] cells/microl versus 633 cells/microl [177] p = 0.004) showed differences with statistical significance. The most important CD4+ count fall was observed at third month after stopping ART; 588 cells/microl (288) on group A and 382 cells/microl (167) on group B. The mean time without ART was 27 months on group A and 7 months on group B. Two patients had acute retroviral syndrome, and one had Pneumocystis jiroveci pneumonia. Cholesterol levels were 199 mg/dl (42) and triglycerides 257 mg/dl (271) on ART and during interruption decreased to 155 (38) and 165 (122) mg/dl respectively. After multivariate analysis, a CD4+ count nadir > 200 cells/microl (p = 0,0005; OR = 0,12; 95% CI, 0.036-0,398) and a CD4+ count at time of ART stop > 800 cells/microl (p = 0,04; OR: 0,11; CI 95%: 0,015-0,936) were independently related to durability of therapy interruption. CONCLUSIONS: Prolonged discontinuation of ART guided by CD4+ response causes a low morbi-mortality. The cell count CD4+ nadir and the CD4+ count at time of ART cessation are protective factors of durability. An improvement of metabolic parameters is observed during the discontinuation of ART.

Interrupción del tratamiento antirretroviral en pacientes con infección crónica por el virus de la inmunodeficiencia humana / Interruption of antiretroviral therapy in chronically HIV-infected patients

Fundamento y objetivo: Describir la evolución inmunológica, virológica y clínica de los pacientes con infección crónica por el virus de la inmunodeficiencia humana (VIH) que suspenden el tratamiento antirretroviral (TAR) de forma prolongada e identificar los factores asociados con la durabilidad de la interrupción. Pacientes y método: Estudio retrospectivo de pacientes que suspenden el TAR tras haber alcanzado recuento de linfocitos CD4+ mayor o igual a 500 células/µl, carga viral del VIH menor o igual a 5.000 copias/ml (3,7 log10) y estabilidad clínica durante al menos 6 meses. Resultados: En octubre de 2004 se incluyeron 44 pacientes; 32 (72%) de ellos continuaban estables sin TAR tras el primer año de interrupción (grupo A) y 12 (28%) pacientes habían precisado reiniciarlo por disminución de los linfocitos CD4+ por debajo de 300 células/µl (grupo B). Entre ambos grupos se observaron diferencias estadísticamente significativas en el nadir de linfocitos CD4+, media (desviación estándar) de 414 (199) células/µl frente a 171 (107) células/µl (p = 0,000) y en los recuentos de linfocitos CD4+ en el momento de la suspensión de TAR, 920 (302) células/µl frente a 633 (177) células/µl (p = 0,004). Tras la interrupción del TAR el descenso más acusado de CD4+ se observó al tercer mes: 588 (288) células/µl para el grupo A y 382 (167) células/µl para el grupo B. La duración media de la interrupción fue de 27 meses en el grupo A y 7 meses en el grupo B. Dos pacientes presentaron síndrome retroviral agudo y otro una neumonía por Pneumocystis jiroveci. Los valores de colesterol con TAR fueron de 199 (42) mg/dl y los de triglicéridos de 257 (271) mg/dl disminuyeron significativamente durante el primer año de seguimiento hasta alcanzar 155 (38) y 165 (122) mg/dl respectivamente. Tras un análisis multivariante, un nadir de linfocitos CD4+ mayor de 200 células/µl (p = 0,0005; odds ratio [OR] = 0,12; intervalo de confianza [IC] del 95% 0,036-0,398) y un valor de linfocitos CD4+ superior a 800 c/µl en el momento de la interrupción de TAR (p = 0,04; OR = 0,11; IC del 95%, 0,015-0,936) se asociaron, de forma independiente, a mayor durabilidad de la suspensión del tratamiento. Conclusiones: Las interrupciones prolongadas del TAR guiadas por la respuesta de linfocitos CD4+ son una estrategia terapéutica que conlleva una baja morbimortalidad. El nadir de linfocitos CD4+ y el valor de linfocitos CD4+ en el momento de la interrupción del TAR pueden predecir la durabilidad de la suspensión. Se observa una mejoría metabólica durante el período libre de TAR

Background and objective: To describe the immunological, virological and clinical outcomes of HIV-infected patients who stop antiretroviral therapy (ART) and to identify the factors related to durability. Patients and method: Retrospective study of patients who interrupt therapy after six months without clinical events, level of CD4+ >= 500 cells/µl and HIV RNA >= 5.000 copies/ml (3,7 log10). Results: In October 2004, 44 patients were included, 32 (72%) of them were stables after one year of ART cessation (group A) and 12 (28%) patients had to restart therapy due to a decreased CD4+ count 200 cells/µl (p = 0,0005; OR = 0,12; 95% CI, 0.036-0,398) and a CD4+ count at time of ART stop > 800 cells/µl (p = 0,04; OR: 0,11; CI 95%: 0,015-0,936) were independently related to durability of therapy interruption. Conclusions: Prolonged discontinuation of ART guided by CD4+ response causes a low morbi-mortality. The cell count CD4+ nadir and the CD4+ count at time of ART cessation are protective factors of durability. An improvement of metabolic parameters is observed during the discontinuation of ART

Estudio prospectivo de casos de leishmaniasis cutánea en soldados acantonados en Montería, 2002 / A prospective study of cases of leishmaniasis cutaneous in soldiers in cantonment

El objetivo de este estudio fue establecer las características clínicas y epidemiológicas de la leishmaniasis cutánea y la respuesta al tratamiento en los soldados de la XI Brigada del ejército en Montería. Se llevó a cabo un estudio prospectivo de casos desde octubre del 2001 a octubre del 2002, en el cual se analizaron las historias clínicas compatibles con leishmaniasis en la XI Brigada. Se incluyeron de forma consecutiva los casos de 67 soldados que habían padecido leishmaniasis, diagnosticada clínicamente por el médico tratante, y dieron su consentimiento para ingresar en el estudio. Por medio de una encuesta aplicada a cada paciente se obtuvieron los datos clínicos y epidemiológicos. Además, a partir de las historias clínicas se obtuvo información del número y el sitio de las lesiones en el cuerpo, la respuesta al tratamiento, el seguimiento y control de la enfermedad y las medidas de prevención aplicadas. Se encontró una frecuencia de casos de leishmaniasis cutánea del 2,3 por ciento. El estudio demostró que algunas zonas del departamento de Córdoba son endémicas para leishmaniasis cutánea, las cuales pueden representar alto riesgo para el personal militar de contraer la enfermedad. El trabajo también mostró la necesidad de adoptar medidas preventivas y extremar la supervisión de la quimioterapia que reciben los soldados

[Abnormal body fat distribution and type of antiretroviral therapy as predictors of cardiovascular disease risk in HIV-infected patients]. / Distribución anormal de la grasa corporal y tipo de tratamiento antirretroviral como predictores de riesgo de enfermedad cardiovascular en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Dyslipidemia, insulin resistance and body fat redistribution are respectively short and long-term complications of protease inhibitor-containing antiretroviral regimens. To establish whether differences in the type of antiretroviral therapy (protease-containing or protease-sparing) or the presence and severity of body fat redistribution, explained differences in cardiovascular risk, we undertook a cross-sectional study. PATIENTS AND METHOD: The study was carried out in 219 consecutive HIV-infected patients attending an outpatient HIV clinic between February and April, 2002. Age, sex, smoking status, weight, height, waist circumference, blood pressure, antihypertensive treatment, total cholesterol, HDL cholesterol, triglycerides, and glucose concentrations, in addition to changes in body fat distribution were measured in 31 HIV-infected patients with no antiretroviral therapy, 35 HIV-infected patients treated with protease inhibitor-sparing regimens, and 153 HIV-infected patients treated with protease inhibitor-containing regimens. A ten-year cardiovascular disease risk was estimated according to the Framingham score. RESULTS: Patients treated with protease inhibitor-containing regimens as well as patients treated with protease inhibitor-sparing agents showed higher concentrations of cholesterol (p < 0.001), triglycerides (p = 0.004), glucose (p = 0.028), and greater changes in body fat distribution (p = 0.001) than patients with no antiretroviral therapy. An abnormal body fat distribution score was more strongly associated (p < 0.001) with the estimated 10-year cardiovascular disease risk than the type of HAART (p = 0.036). Ten-year cardiovascular disease risk increased linearly from 7.48% to 11.16% and to 19.50% in patients with no or mild, moderate and severe lipodystrophy scores, respectively. CONCLUSIONS: The results of this study encourage the use of cardiovascular preventive strategies in HIV-infected patients with severe lipodystrophy.

Distribución anormal de la grasa corporal y tipo de tratamiento antirretroviral como predictores de riesgo de enfermedad cardiovascular en pacientes infectados por el virus de la inmunodeficiencia humana / Abnormal body fat distribution and type of antiretroviral therapy as predictors of cardiovascular disease risk in HIV-infected patients

FUNDAMENTO Y OBJETIVO: La dislipemia, la resistencia a la insulina y la redistribución de la grasa corporal son, respectivamente, complicaciones a corto y largo plazo atribuidas principalmente al tratamiento antirretroviral con inhibidores de la proteasa. Para determinar si la diferencia entre el tipo de tratamiento antirretroviral (con o sin inhibidores de la proteasa) o la presencia e intensidad de la redistribución de la grasa corporal explican diferencias en el riesgo cardiovascular llevamos a cabo un estudio transversal. PACIENTES Y MÉTODO: El estudio se realizó en 219 pacientes infectados por el virus de la inmunodeficiencia humana (VIH) consecutivamente atendidos en consulta entre febrero y abril de 2002. Las variables analizadas incluyeron edad, sexo, condición de fumador, peso, talla, perímetro de cintura, presión arterial, tratamiento contra la hipertensión, colesterol total, colesterol unido a lipoproteínas de alta densidad, triglicéridos y glucemia, así como alteraciones en la distribución de grasa corporal (evaluada por el propio paciente de 0 a 3 puntos en 6 áreas corporales) en un total de 31 pacientes sin tratamiento antirretroviral, 35 pacientes tratados con regímenes sin inhibidores de la proteasa y 153 pacientes tratados con regímenes con inhibidores de la proteasa. Se estimó el riesgo cardiovascular a los 10 años en cada paciente según la puntuación de Framingham. RESULTADOS: Los pacientes que recibían tratamiento antirretroviral (con y sin inhibidores de la proteasa) presentaron mayores concentraciones de colesterol total (p < 0,001), triglicéridos (p = 0,004) y glucosa (p = 0,028) y mayor alteración en la distribución de la grasa corporal (p = 0,001) que los pacientes sin tratamiento antirretroviral. La alteración en la distribución de la grasa corporal tuvo una asociación mayor (p < 0,001) con el riesgo cardiovascular que el tipo de tratamiento antirretroviral (p = 0,036). El riesgo cardiovascular estimado a los 10 años se incrementó linealmente del 7,48 al 11,16 y al 19,50 por ciento en los pacientes con redistribución leve, moderada o importante de la grasa corporal, respectivamente. CONCLUSIONES: Este estudio muestra la necesidad de utilizar estrategias de prevención del riesgo cardiovascular en pacientes con redistribución importante de la grasa corporal (AU)

Risk and determinants of developing severe liver toxicity during therapy with nevirapine-and efavirenz-containing regimens in HIV-infected patients.

We examined the risk and determinants of developing severe liver toxicity in 108 HIV-infected patients showing adherence to nevirapine- and efavirenz-containing regimens. Between January 1997 and December 2000, 70 patients were treated with nevirapine- and 38 patients with efavirenz-containing regimens, for a median period of 127 days (interquartile range 65-240). Severe liver toxicity was defined as grade 3-4 elevations (>5 x upper limit of normal) of aminotransferases AST or ALT. A total of 22 (20%) patients showed severe liver toxicity, 17 of them were treated with nevirapine- and five with efavirenz-containing regimens (relative risk [RR]: 1.85, 95% confidence intervals [CIs] 0.74-4.61; P=not significant). Multivariate analysis showed the association of severe liver toxicity with hepatitis C antibody positive (RR 7.64; 95% CI: 1.48-39.52; P=0.01), nevirapine- or efavirenz-containing regimens combined with a protease inhibitor (RR: 3.07, 95% CI: 1.01-9.32, P=0.04) and alcohol intake greater than 40 g per day (RR: 3.09, 95% CI: 1.27-7.54, P=0.01). These findings have potential implications for selecting and monitoring antiretroviral therapy in HIV-infected patients with hepatitis C virus coinfection and for avoiding alcohol intake during antiretroviral therapy.