Generalized Linear Model (GLM) framework for the association of host variables and viral strains with liver fibrosis in HCV/HIV coinfected patients.

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.

Relating the liver damage with hepatitis C virus polymorphism in core region and human variables in HIV-1-coinfected patients.

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.

Bacteriemia por anaerobios estrictos: estudio de 68 pacientes / Anaerobic bloodstream infections: Study of 68 episodes

Introducción Existe controversia en la literatura médica sobre la bacteriemia por anaerobios: algunos autores detectaron en las últimas décadas un aumento de su incidencia, y otros, una franca disminución, e incluso se ha propuesto el no hacer de forma habitual hemocultivos para anaerobios. Presentamos un análisis prospectivo de los casos de bacteriemia por anaerobios diagnosticados en nuestro centro entre enero de 2003 y mayo de 2008.ResultadosSe identificaron 68 pacientes con bacteriemia verdadera por anaerobios estrictos. La edad media fue de 64±19 años. La mayoría (63,2%) tenía al menos una comorbilidad, en el 20,6% de los casos fue una neoplasia sólida frecuentemente relacionada con el tracto digestivo. El foco principal de la bacteriemia fue abdominal (42,6%). Los gérmenes más frecuentemente aislados fueron diversas especies del grupo Bacteroides fragilis (36,7%), Clostridium spp. (17,6%), Peptostreptococcus spp. (16,1%) y Prevotella spp. (16,1%). El tratamiento antibiótico empírico más utilizado fue un carbapenémico en el 35,3% de los casos y se utilizó biterapia en el 30,9%. En la mayoría de los casos el tratamiento antibiótico empírico fue adecuado. La mortalidad bruta fue del 23,5% y directamente relacionada con la bacteriemia (9,2%). La presencia de sepsis, shock séptico o un score de Pitt mayor de 4 fueron predictores de mortalidad. Conclusiones La incidencia de bacteriemia por anaerobios en nuestro centro se cifra en 0,89 casos/1.000 ingresos hospitalarios. Los pacientes de mayor riesgo son los ancianos con diferentes comorbilidades o con procesos oncológicos; la mortalidad fue elevada (AU)

Introduction There is some controversy regarding the current rates of anaerobic bacteremia. Some authors have described an increasing incidence in recent years, whereas others report declining rates. There is even debate over whether to routinely perform anaerobic blood cultures. We present a prospective analysis of anaerobic bloodstream infections diagnosed at our medical center from January 2003 to May 2008.ResultsSixty-eight patients had bloodstream infection caused exclusively by anaerobic bacteria. Median age was 64±19 years and 63.2% had at least one comorbid condition, including 20.6% with a solid neoplasm, often related to the gastrointestinal tract. The main focus of anaerobic bacteremia was the abdomen (42.6%). The most common isolates were several species from the Bacteroides fragilis group (36.7%), Clostridium spp. (17.6%), Peptostreptococcus spp. (16.1%), and Prevotella spp. (16.1%). Empirical antimicrobial treatment was adequate in 69.1%. Overall mortality was 23.5%, and bacteremia-related mortality was 9.2%. Sepsis, septic shock, and a Pitt score >4 were independent predictors of mortality. Conclusions The incidence of anaerobic bacteremia in our hospital was 0.89 cases per 1000 hospital admissions. Patients at high risk were elderly persons with associated underlying diseases including malignant disease. Mortality was high (AU)

[Anaerobic bloodstream infections: study of 68 episodes]. / Bacteriemia por anaerobios estrictos: estudio de 68 pacientes.

INTRODUCTION: There is some controversy regarding the current rates of anaerobic bacteremia. Some authors have described an increasing incidence in recent years, whereas others report declining rates. There is even debate over whether to routinely perform anaerobic blood cultures. We present a prospective analysis of anaerobic bloodstream infections diagnosed at our medical center from January 2003 to May 2008. RESULTS: Sixty-eight patients had bloodstream infection caused exclusively by anaerobic bacteria. Median age was 64+/-19 years and 63.2% had at least one comorbid condition, including 20.6% with a solid neoplasm, often related to the gastrointestinal tract. The main focus of anaerobic bacteremia was the abdomen (42.6%). The most common isolates were several species from the Bacteroides fragilis group (36.7%), Clostridium spp. (17.6%), Peptostreptococcus spp. (16.1%), and Prevotella spp. (16.1%). Empirical antimicrobial treatment was adequate in 69.1%. Overall mortality was 23.5%, and bacteremia-related mortality was 9.2%. Sepsis, septic shock, and a Pitt score >4 were independent predictors of mortality. CONCLUSIONS: The incidence of anaerobic bacteremia in our hospital was 0.89 cases per 1000 hospital admissions. Patients at high risk were elderly persons with associated underlying diseases including malignant disease. Mortality was high.

Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients.

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.

Effects of escin on indinavir crystallization time in the urine of patients with HIV-I infection: a multicenter, randomized, open-label, controlled, four-period crossover trial.

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.