[Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection]. / Ensayo clínico comparativo de eficacia y seguridad de cuatro pautas de tratamiento antirretroviral de alta eficacia (TARGA) en pacientes naive con infección por VIH avanzada.

BACKGROUND: Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive. PATIENTS AND METHODS: Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks. RESULTS: A total of 98 patients with a mean baseline CD4 count of 122 x 10(6)/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients. CONCLUSIONS: In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI.

Ensayo clínico comparativo de eficacia y seguridad de cuatro pautas de tratamiento antirretroviral de alta eficacia (TARGA) en pacientes naive con infección por VIH avanzada / Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection

Introducción. Comparación de la eficacia y seguridad de cuatro pautas de terapia antirretroviral de gran actividad (TARGA) incluyendo dos análogos de nucleósidos (AN) y un inhibidor de proteasa (IP) en pacientes con el virus de la inmunodeficiencia humana (VIH) con infección avanzada y naive a antirretrovirales. Pacientes y método. Ensayo clínico, multicéntrico, randomizado y abierto en diez hospitales comunitarios de Castilla-La Mancha y Madrid. La pauta 1 contenía zidovudina (ZDV), lamivudina (3TC) e indinavir (IDV); la pauta 2 incluía ZDV, 3TC y ritonavir (RTV); la pauta 3 era didanosina (DDI), estavudina (D4T) e IDV, y la pauta 4 incluía DDI, D4T y RTV. Se ha valorado como variable principal de respuesta el descenso de la carga viral del VIH (CV), y como variables secundarias: el aumento del número de linfocitos CD4, el porcentaje de progresión de la enfermedad, las reacciones adversas y la adherencia. Las determinaciones se realizaron en la visita basal y a las 6, 12, 24, 36 y 48 semanas. Resultados. Se incluyeron 98 pacientes con una media de CD4 basal de 122 x 106/l (rango de 5-340) y una carga viral basal de 5,1 log copias/ml. A las 48 semanas, en el análisis de los pacientes en tratamiento se observó un incremento medio de los CD4 y una disminución de la carga viral sin diferencia significativa entre las 4 pautas (103 células/2,62 log en la pauta 1, 169 células/ 2,86 log en la pauta 2, 171 células/2,56 log en la pauta 3 y 141 células/1,71 log en la pauta 4). Interrumpieron el tratamiento por reacciones adversas: el 24% en la pauta 1, el 48% en la pauta 2, el 26% en la pauta 3 y el 32% en la pauta 4, sin diferencias significativas. Analizando por grupos de IP el 41% de los pacientes con RTV y el 25% de los pacientes con IDV suspendieron el tratamiento por efectos adversos. Se produjo retirada del tratamiento por progresión de la enfermedad en el 7% de los pacientes con RTV y en el 9% de los pacientes con IDV. Conclusiones. En los pacientes VIH positivos con infección avanzada la eficacia entre cuatro pautas de TARGA es similar, pero existe una tendencia a precisar mayor retirada por efectos adversos en los grupos de RTV que en los de IDV, los dos usados como IP único

Background. Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive. Patients and methods. Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks. Results. A total of 98 patients with a mean baseline CD4 count of 122 x 106/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients. Conclusions. In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI

[Best result of digoxin dosing in the aged by taking into account that both the elimination as well as the volume of distribution of the drug decrease when the kidney function deteriorates]. / Mejor resultado del ajuste de la dosis de digoxina en ancianos si se tiene en cuenta que tanto la eliminación como el volumen de distribución del fármaco disminuyen cuando se reduce la función renal.

PURPOSE: To evaluate three methods for digoxin dose adjustment in aged patients. METHODS: We determined the plasma digoxin levels that would be attained in 87 old patients with doses adjusted to the kidney function by means of three separate procedures. RESULTS: Age: 79.0 "6.3 years of age; creatinin clearance (Clc): 0.70" 0.23 ml/Kg of lean body weight and minute. Only the methods that adjust both the digoxin clearance and the volume of distribution to the Clc achieve the independence between the digoxinemia and the kidney function. The best of them, by calculating the elimination constant (K) and the volume of distribution (V) as linear functions of the Clc, so that K ranges between 0.173 and 0.462 days-1 and V between 4 and 10 l/Kg of lean body weight when the Clc varies from 0 to 110 ml/minute, achieve digoxinemia figures between 0.8 y 2.0 ng/ml and above 2.0 ng/ml in the 81.6% and 0.0% of the patients (95% confidence intervals (95% CI): 72.2% to 88.4 and 0.0% to 4.6%), respectively; with a precision and a bias of 0.43 and -0.06 ng/ml (95% CI: 0.38 to 0.48 and -0.16 to 0.03 ng/ml), respectively. CONCLUSION: The described method would lead to good results if digoxin has not been prescribed in order to control the cardiac frequency in the setting of auricular fibrilation.

[Predictive capacity of 3 methods for estimating the maintenance dose of digoxin in elderly patients]. / Capacidad predictiva de tres métodos de cálculo de la dosis de mantenimiento de digoxina en ancianos.

PURPOSE: To evaluate three methods for digoxin dose adjustment in aged patients. METHODS: We determined the plasma digoxin levels that would be attained in 47 consecutive old patients with doses adjusted to the creatinin clearance (Clc) by means of three mathematical functions. RESULTS: Age: 79.1 +/- 6.1 years of age; Clc: 0.77 +/- 0.24 mL/kg of lean body weight and minute. Once the dose has been fitted to the digoxin pharmacokinetic parameters described in the bibliography, the drug levels would oscillate between 0.8 and 2.0 ng/mL in 85.1% of the patients, with a 95% confidence interval (95% CI) from 72.3% to 92.6%; in 0.0% of the patients the levels would be greater than 2 ng/mL (95% IC: 0.0% to 7.6%). The precision and the bias would be 0.40 ng/mL (95% IC: 0.33 to 0.46 ng/mL) and--0.08 ng/m (95% IC: -0.19 to 0.04 ng/mL), respectively. The drug level would not be associated with the Clc (coefficient of Clc in the regression line: -0.0003; P > 0.9). The results would be worse with the others two mathematical functions. CONCLUSION: The first of the above adjustment methods would lead to good results if digoxin has not been prescriped in order to control the cardiac frequency in the setting of auricular fibrillation.

[Extrapyramidal toxicity caused by metoclopramide and clebopride: study of voluntary notifications of adverse effects to the Spanish Drug Surveillance System]. / Toxicidad extrapiramidal a metoclopramida y a cleboprida: estudio de las notificaciones voluntarias de reacciones adversas al Sistema Español de Farmacovigilancia.

OBJECTIVE: To clarify if there is any basis for the hypothesis that Clebopride leads to more extrapyramidal reactions than Metoclopramide. DESIGN: Observational, longitudinal, retrospective and comparative study of two series of cases. SETTING: The entire Spanish healthcare system. PATIENTS: Those notified to the Spanish Drug watch system as possibly having suffered an adverse reaction to Metoclopramide (n = 98) or Clebopride (n = 123) between 1/1/1990 and 10/6/1997. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 84.3% of suspected adverse reactions to Clebopride and 51.6% of those to Metoclopramide had a non-hospital precedence (P < 0.001). In 48.0% of suspected adverse reactions to Metoclopramide and 72.4% of those to Clebopride, there was extrapyramidal toxicity (P = 0.021). CONCLUSIONS: There is a basis for the hypothesis that Clebopride causes more extrapyramidal reactions than Metoclopramide. It was reasonable to realize a study based on this hypothesis.