[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