Interacciones graves o potencialmente letales entre antirretrovirales y otros medicamentos / Severe or life-threatening interactions between antiretrovirals and non-HIV drugs

El tratamiento antirretroviral de gran actividad (TARGA) ha permitido un buen control de la infección por VIH, y por lo tanto la población afectada envejece progresivamente y la esperanza de vida va siendo parecida a la de la población general. Por otro lado, se sabe que la infección por VIH predispone, incluso en pacientes con TARGA efectivo, a un mayor riesgo cardiovascular y a una mayor incidencia de algunas neoplasias. Por todo ello, la mayor parte de pacientes infectados por el VIH reciben diversos medicamentos (pautados por el facultativo o autoadministrados) además de los antirretrovirales. Este artículo revisa las interacciones que pueden provocar daños importantes o incluso poner en peligro la vida de los pacientes y que los clínicos —sobre todo los que no manejan directamente pacientes infectados por el VIH— tendrían que conocer. También se revisan las implicaciones de las interacciones entre antirretrovirales y otros fármacos en situaciones especiales, como la administración concomitante de citostáticos, inmuno-supresores utilizados en el trasplante de órganos sólidos o pacientes que reciben los nuevos tratamientos para el virus de la hepatitis C. En general, las pautas con 2 inhibidores nucleós(t)idos de la transcriptasa inversa con raltegravir o dolutegravir son las que tienen menos potencial de interacciones clínicamente significativas (AU)

Highly active antiretroviral therapy has helped to improved control of the HIV infection, and has led to a progressively older population with the infection having a life expectancy quite similar to that of the general population. On the other hand, it is also known that HIV infection, even in patients with undetectable viral loads and good immunity, carries an increased cardiovascular risk, as well as an increased incidence of certain cancers. Therefore, the majority of HIV-infected patients receive several drugs (either prescribed by the physician or self-administered) combined with antiretrovirals. This article reviews the interactions between antiretrovirals and other drugs that can cause significant damage to patients, or even be life-threatening and of whom clinicians, especially those not directly treating HIV-infected patients, should be aware. A review is also presented on the implications of interactions between antiretrovirals and other drugs in special situations, such as the co-administration with cytostatics, immunesuppressants used in solid organ transplantation, or patients receiving new treatments for hepatitis C. Generally, combinations with two nucleos(t)ide reverse transcriptase inhibitors and raltegravir (or in the near future, dolutegravir) are those with less potential for clinically significant interactions (AU)

Efectos adversos de atazanavir / Adverse effects of atazanavir

Atazanavir es un fármaco que inhibe la proteasa del virus de la inmunodeficiencia humana (VIH) con muchas de las características de otros inhibidores de la proteasa y algunas ventajas sobre éstos, como la posología sólo una vez al día, la baja carga de comprimidos, la menor alteración gastrointestinal y un perfil metabólico más favorable, incluida la alteración del metabolismo de los hidratos de carbono. La hiperbilirrubinemia y la ictericia secundaria son su principal efecto adverso, aunque en raras ocasiones lleva a la suspensión del fármaco. Otros efectos adversos, como la nefrolitiasis o las alteraciones electrocardiográficas, son francamente raras

Atazanavir is a drug that inhibits HIV protease. It has many of the characteristics of other protease inhibitors and also some advantages over these, such as the single dose of once per day, low capsule load, less gastrointestinal problems and a very friendly metabolic profile, including carbohydrate metabolism. Secondary high plasma bilirubin and jaundice are its main adverse effect which only on rare occasions requires stopping the drug. Other adverse effects, such as nephrolithiasis or ECG changes are extremely rare

Perfil lipídico de atazanavir / Lipid profile of atazanavir

En la actualidad se sabe que la exposición al tratamiento antirretroviral, particularmente a los inhibidores de proteasa clásicos, se asocia con un incremento del riesgo de presentar enfermedad cardiovascular, aunque la interrupción del tratamiento antirretroviral puede ocasionar un riesgo aún mayor. Se han emitido recomendaciones sobre la intervención ante la dislipidemia y el riesgo cardiovascular en personas seropositivas. Estas recomendaciones se semejan a las de la población general, pero incluyen el carácter particular de considerar incluir un tratamiento antirretroviral benigno con los lípidos en la medida de lo posible. Atazanavir presenta unas características diferentes de las de otros inhibidores de la proteasa en cuanto a sus efectos sobre el tejido adiposo y el metabolismo en general. Atazanavir no se ha asociado con los aumentos de las concentraciones de colesterol total, colesterol unido a lipoproteínas de baja densidad (cLDL) o triglicéridos que han presentado otros inhibidores de la proteasa en pautas de inicio, rescate o simplificación. Los resultados de los estudios in vitro y clínicos son claros y contundentes. Estas características le confieren un papel singular muy atractivo a la hora de decidir el tratamiento antirretroviral más adecuado para una proporción de pacientes infectados por el virus de la inmunodeficiencia humana (VIH) en los que la reducción del riesgo cardiovascular constituya una prioridad

It is currently known that exposure to antiretroviral treatment, particularly to the classic protease inhibitors, is associated with an increased risk of suffering from cardiovascular disease, although stopping antiretroviral treatment can cause an even greater risk. Recommendations have been made on how to deal with dyslipaemia and cardiovascular risk in seropositive patients. These recommendations are similar to those for the general population, but include the particular feature of considering including benign treatment with lipids wherever possible. Atazanavir has different characteristics from other protease inhibitors as regards its effects on adipose tissue and metabolism in general. Atazanavir is not associated with increases in total cholesterol, LDL-cholesterol or triglycerides as with other PI in initial, rescue or simplification therapy. The results of in vitro studies and clinical studies are clear and convincing. These characteristics give it a particular role that is very attractive when deciding the most suitable antiretroviral treatment for a proportion of HIV-infected patients in whom the reduction in cardiovascular risk is seen as a priority

Safety and efficacy of reduced doses of ritonavir (RTV) plus saquinavir (SQV) in the treatment of AIDS patients in Brazil

The use of reduced doses of Ritonavir (RIT) and Saquinavir (SQV) is considered a potent alternative in treating patients infected by HIV-1. We tested a combination of 300mg of RIT plus 600mg of SQV, twice daily, in association with two reverse transcriptase inhibitors to treat AIDS patients for a period of 6 monts. Evaluation of HIV-1 RNA plasma levels, CD4+/CD8+ cell count and biochemical/hematological parameters (liver enzymes, serum electrolytes, creatinin, blood glucose, uric acid, white blood cell count, platelet count, and hemoglobin level) were performed after 30, 90 and 180 days of therapy. Clinical failure and adverse reactions were also recorded in order to assess safety and efficacy of the treatment. A total of 30 AIDS patients (25 male; 5 female) were enrolled in the study. Eight patients discontinuede the therapy due to intolerance, 2 patients presented clinical failure (onset of AIDS defining events during the study period), 2 patients were excluded due to protocol violation. Five patients tolerated only a lower dose of RIT (400mg/day). Patients who completed 6 months of therapy had a drop in viral load from 4.8ñ.7log10median4.9log) to 3.4ñ1.0log10(median 2.6log), and an increase in CD4+ count from 109ñ86 cells/ml(median 84 cells/ml) to 249ñ114 cells/ml(median 265cells/ml), compared to baseline values. However, patients who used a lower dose of RIT (400mg/day) had a less impressive drop in viral load values(mean0.6log10RNA copies/ml) when compared with those using the 600mg/day of the drug(mean 2.4log10). The percentage of patients presenting undetectable levels of HIV-1 RNA in plasma was quite different for the 2 groups: 92 percent of patients with a viral load <400 RNA copies/ml were using 600mg of RIT. The combination of reduced doses of RIT and SQV reduced viral load >1.0log10 after 6 months in 83 percent of study patients. The dose of 600mg/day of RIT was more effective in reducing viral load than 400mg/day, but was less well-tolerated. CD4+ cell counts increased in all patients regardless of the RIT dose used.