Inhibidores de la proteasa del vih: actualización y monitorización terapéutica de las concentraciones plásmaticas en el tratamiento antirretroviral / HIV protease inhibitors: update and therapeutic monitoring of plasma concentration during anti-retroviral therapy

La incorporación de los inhibidores de la proteasa (saquinavir, ritonavir, indinavir, nelfinavir) en la terapia antirretroviral ha supuesto un importante descenso en la morbilidad y mortalidad provocada por el SIDA. Son compuestos no peptídicos que inhiben de forma potente y selectiva la proteasa del VIH-1. Se caracterizan por tener en común un metabolismo de eliminación hepático y una semivida de eliminación corta, con diferencias en el ámbito de absorción y distribución. Excepto el indinavir, deben administrarse con comidas. Poseen distintos perfiles de toxicidad, siendo el ritonavir el que presenta una mayor incidencia de reacciones adversas. La extensa metabolización por la isoenzima CYP3A4 del citocromo P450 puede originar interacciones de interés clínico. Actualmente, la carga viral y linfocitos T CD4 son los marcadores de evolución clínica de la enfermedad. Recientes estudios sugieren que la monitorización de las concentraciones plasmáticas pueden ser de utilidad en casos de no-adherencia, interacciones farmacocinéticas y fracaso virológico (AU)

[Cerebral toxoplasmosis]. / Toxoplasmosis cerebral.

Toxoplasmic encephalitis is associated with high mortality and morbidity and still presents a notable incidence in our setting. Neither the clinical symptoms nor radiological features are diagnostic of this disease; however, because of its frequency and clinical importance, specific treatment is begun whenever toxoplasmosis is suspected. In patients with negative serology, or who are receiving adequate prophylaxis, or who do not respond to 2 weeks of treatment, or who present radiological lesions suggestive of another illness, diagnosis should not be delayed, and brain biopsy should be considered as soon as possible. In these cases, SPECT with 201TI (sensitivity and specificity over 90-95% for lymphoma) and/or the PCR technique to detect T. gondii (sensitivity 50-65% and specificity 95-100%) or Epstein-Barr virus (sensitivity 70-80% and specificity 95% for lymphoma) can be very useful. The treatment of choice is pyrimethamine (100 mg the first day followed by 50 mg/day) and sulphadiazine (1-1.5 g/6 h) during 6-8 weeks. If the patient is allergic to sulfadiazine and cannot be desensitized the regimen of choice is pyrimethamine and clindamycin (600 mg/6 h), with similar efficacy. Clinical experience with other therapeutic alternatives is limited. Pyrimethamine can be associated with clarithromycin (0.5-1 g/12 h), azithromycin (1-1.5 g/day) atovaquone (750 mg/6 h), dapsone (100 mg/day) or doxycyclin (200 mg/12 h). Cotrimoxazole or clindamycin can be administered intravenously to patients who cannot receive enteral treatment. The toxicity of these therapeutic regimens is significant and treatment has to be suspended in 10-40% of cases. The interactions that can be produced with other drugs used to treat HIV-infected patients are generally of little clinical relevance.

[Acute abdomen secondary to cytomegalovirus infection]. / Abdomen agudo secundario a infección por citomegalovirus.

A case of a HIV-positive patient hospitalized with acute abdomen secondary to infection by cytomegalovirus (CMV), is presented. Infection by CMV is frequent in HIV-positive patients, with a relevant intestinal affection. However, its presentation as acute abdomen is more rare, although it has to be considered given that the demonstration of the presence of CMV and its potential pathogenic power have important therapeutic connotations. Currently, the use of diagnostic techniques based in specific monoclonal antibodies and DNA hybridization methods increases the diagnostic sensitivity of the traditional methods based on histological demonstration of the cytopathic effect and/or viral cultives.