Tipo de mutaciones del VIH en pacientes con terapia antirretroviral en el Hospital Nacional Edgardo Rebagliati Martins. 2009-2012 / Type of mutations of HIV in patients with antiretroviral therapy at the National Hospital Edgardo Rebagliati Martins. 2009-2012

La resistencia limita la efectividad de la terapia antirretroviral. En el HNERM, hay acceso a la terapia anti-retroviral altamente activa, pero no existe información sobre la frecuencia de mutaciones asociadas a resistencia a los medicamentos. Objetivo: Determinar las mutaciones más comunes asociadas a resistencia a los medicamentos anti-retrovirales en pacientes infectados con VIH que recibían tratamiento previo en el HNERM. Materiales y métodos: estudio retrospectivo de análisis del genotipo de 124 pacientes de 6 a 90 años (74.19 por ciento varones) con terapia antirretroviral. El análisis se realizó utilizando el kit de genotipado TRUGENE HIV-1 y el sistema de secuenciación de ADN OpenGene Trugene HIV-1. Resultados: Mediana de carga viral 34 852.5 RNA copias/ml. La frecuencia de la resistencia a los inhibidores de la RT análogos de los nucleósidos (INTR), a los inhibidores no análogos de los nucleósidos RT (INNTR) y a los inhibidores de la proteasa (IP) fue de 43.6 por ciento, 39.64 por ciento y 45.77 por ciento, respectivamente. Las mutaciones más frecuentes encontradas fueron M184V (62.9 por ciento), K103N (33.8 por ciento), V118I (26.6 por ciento), M36I (35.4 por ciento), I93L (33.8 por ciento), y M46I (27.4 por ciento). Durante los cuatro años del estudio, hubo un aumento significativo en la resistencia de los INNTR. Conclusiones: Estos datos proporciona información importante sobre la epidemiología de mutaciones de resistencia de la droga y debe ayudar a diseñar nuevas estrategias.

Resistance limits the effectiveness of anti-retroviral therapy. In HNERM, there is free access to highly active anti-retroviral therapy, but there is no information about the frequency of mutations associated to drug resistance. Aim: To determine the most common mutations associated with resistance to the anti-retroviral drug in patients with HIV who received pre-treatment in HNERM. Materials and Methods: Retrospective study of 124 genotype analysis coming from patients aged 6 to 90 years (74.19 per cent males) with virological failure. The anaIysis was performed using the kit Trugene HIV-1 and the system of DNA sequencing OpenGene Trugene HIV-1. Results: Mean viral load were 34 852.5 RNA copies/mI, respectively. The frequency of resistance to nucleoside RT inhibitors (NRTI), non nucleoside RT inhibitors (NNRTI) and protease inhibitors (PI) was 43.6 per cent, 39.64 per cent and 45.77 per cent, respectively. The most common mutations found were M184V (62.9 per cent), K103N (33.8 per cent), V118I (26.6 per cent), M36I (35.4 per cent), I93L (33.8 per cent), y M46I (27.4 per cent). During the four years of the study, there was a significant increase in NNRTI resistance. Conclusions: These data provides important information about the epidemiology of drug resistance mutations and should help to design new strategies.

Comparison between sprague-dawley and wistar rats as an experimental model of pharmacokinetic alterations induced by spinal cord injury

Two strains of rats, Sprague-Dawley and Wistar, were assayed in order to determine which strain is the more suitable experimental model for the study of pharmacokinetic alterations inuced by spinal cord injury. Animals were submitted to spinal cord contusion at the T8-T9 level by the weight drop method. A single acetaminophen oral dose (100 mg/kg) was administered 24 h after injury and blood samples were drawn for a period of 4 h. Acetaminophen concentration in whole blood was determined by high performance liquid chromatography and pharmacokinetic parameters were estimated. For both strains, Cmax and AUC were significantly lower, whereas tmax remained uchanged, in injured animals compared to sham-injured controls. Circulating acetaminophen concentrations were higher; therefore, pharmacokinetic alterations were more easily discerned, in Sprague-Dawley than in Wistar rats. It is concluded that the Sprague-Dawley strain is a more suitable model for the study of pharmacokinetic alternations induced by spinal cord injury