Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART.

Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM's in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM's during STI.

Expression of CCR5, CXCR4 and DC-SIGN in Cervix of HIV-1 Heterosexually Infected Mexican Women.

BACKGROUND: A number of studies have demonstrated that receptor and co-receptor expression levels which may affect viral entry, promoting cervical HIV infection. The aim was to evaluate the expression levels of CCR5, CXCR4and DC-SIGN mRNA in a sample of heterosexually HIV infected Mexican women. METHODS: We enrolled twenty-six HIV heterosexual infected women attending a local infectious diseases medical unit.RNA was isolated from the cervix and gene expression analysis was performed using real-time PCR. RESULTS: Expression rates for mRNA of CCR5 (median 1.82; range 0.003-2934) were higher than those observed for CXCR4 (0.79; 0.0061-3312) and DC-SIGN (0.33; 0.006-532) receptors (p < 0.05). A high correlation was found between the mRNA expression levels of these three receptors (rs = 0.52 to 0.85, p < 0.01). CONCLUSION: Levels of expression of the tested chemokine receptors in the cervix are different from each other and alsovary from woman to woman, and seem to support the suggestion that chemokine receptor expression in genital tissues may be playing a role in the HIV transmission.

Distribution of HCV genotypes and HCV RNA viral load in different regions of Mexico.

BACKGROUND AND AIM: To identify the geographic distribution of hepatitis C virus (HCV) genotypes and HCV RNA viral load in a large number of HCV-infected carriers in Mexico. METHODS: Patients with chronic hepatitis C (n = 8,802) were studied to identify HCV genotype using an immune line probe assay in samples shown previously to be positive for viral RNA by an RT-PCR test. Baseline HCV RNA was also evaluated. RESULTS: Genotype 1 accounted for 70.3%, genotype 2 for 21.8%, genotype 3 for 7.2%, genotype 4 for 0.3%, and genotype 5 for 0.1% of all cases; coinfection was present in 0.3%. Overall, Genotype 1 was the most prevalent Genotype. Regionally, genotype 1 occurred more frequently in the North-East, North, and Center- East regions of Mexico; genotype 2 was more prevalent in the South, East, and Peninsula regions; and genotype 3 was more prevalent in the North and North-West regions. Only 22.4% of patients with genotype 1 were classified in the low HCV RNA viral load category, and the distribution of this genotype did not differ significantly between regions. CONCLUSION: The prevalence of HCV genotypes and viral load in Mexico was 70.3% for genotype 1, but only 22.4% of these patients had a low HCV viral load. Distribution was not uniform in Mexico, with greater frequency of genotype 2 in South, East and Peninsula Regions and Genotype 3 in North and North-West Regions.

Expression of DC-SIGN in peripheral blood dendritic cells of patients with typical, slow, and rapid progression to AIDS.

The main access route for human immunodeficiency virus (HIV) into the lymph nodes is through the mucosa. Once there, dendritic cells (DCs) are the first cells to interact with the virus. Then, DCs can uptake and transport to the lymph nodes, beginning a disseminated infection. Interaction between the virus and DCs is mediated by the receptor DC-SIGN. This study seeks to determine any relationship between HIV-AIDS immunopathology and DC-SIGN expression levels in DCs from typical, rapid, and slow progressors. A DC separation system was implemented using peripheral blood mononuclear cells from infected subjects. The study included 27 patients classified as typical, rapid, and slow progressors according to their clinical and epidemiological files. Finally, quantification of DC-SIGN was achieved by real-time PCR and by applying the Relative Quantification Scheme (DeltaDeltaCt). We isolated DCs from peripheral blood of 27 HIV-infected patients. Nineteen were considered as typical progressors, five as slow progressors, and three as rapid progressors. No significant differences were observed on the expression levels of DC-SIGN among the three groups of patients. Even if there are differences in expression levels among the analyzed patients, we did not find any significant differences in DC-SIGN expression among the three included groups. We therefore cannot conclude that the expression level of the receptor is related with the progression to AIDS.

Tratamiento de la candiduria en pacientes en estado crítico: estudio comparativo entre fluconazol vía oral y anfotericina B en irrigación / Treatment of candiduria in the critically ill: comparative study between oral fluconazole and irrigated amphotericin B

La participación de origen micótico en el desarrollo de infecciones nosocomiales se ha incrementado de 1980 a 1990 de 6 a 10.4 por ciento en todos los sitios de infección. Para el tracto urinario la incidencia se ha elevado de 6.7 a 18.7 por ciento. Se compara la eficiencia y seguridad del fluconazol contra anfotericina B para erradicación de candiduria en pacientes en estado crítico: 1) fluconazol, 100 mg vía oral o vía sonda nasogástrica cada 12 horas, 2) anfotericina B, 25 mg en 1000 mL en solución de agua bidestilada para irrigación vesical continua cada 24 horas. Se trataron 15 pacientes por grupo. No hay diferencia entre ambas modalidades terapéuticas en el tiempo de erradicación de la funguria (p<0.05 t de student). En el grupo de irrigación vesical continua se presentó 20 por ciento de espisodios de fungemia, con deterioro clínico y aumento en la permanencia en la unidad. No se demostraron efectos colaterales en ninguna de las modalidades terapéuticas. Ante la posibilidad de diseminación o de estar tratando tópicamente un problema sistémico no se recomienda en este grupo de pacientes el empleo de anfotericina B en irrigación

El gasto energético en reposo, medido contra estimado, en pacientes críticamente enfermos / Energy consumed vs estimated energy expenditure at rest in critically ill patients

Se determinaron las diferencias entre el método de calorimetría indirecta (Ci) y el método de Harris-Benedict, para la evaluación de los requerimientos calóricos en pacientes críticamente enfermos, utilizándose un procedimiento manual en la Ci. Se evaluaron 40 pacientes por ambos métodos. En el método de Harris-Benedict, se añadieron factores de actividad y lesión de acuerdo a cada caso. La Ci se basó en el análisis de gases (O2 y CO2) de una muestra de aire inspirado y expirado por el paciente, mediante las ecuacions de Weir y las tablas de Lusk. El análisis de calorimetría indirecta contra Harris-Benedict solo, es decir, sin factor de actividad o lesión, no presentó diferencias estadísticamente significativas. Los resultados mostraron diferencias estadísticamente significativas cuando se compararon calorimetría indirecta (p>0.05 y p>0.001, respectivamente). Harris-Benedict no mostró una correlación apropiada en estos pacientes, concordando con lo reportado en la literatura. El procedimiento de medición calorimétrica empleada, tiene validez, y puede ser utilizado en todo hospital de segundo nivel de atención