[Immunological effectiveness of the nucleoside/nucleotide analog combinations, tenofovir + lamivudine, didanosine + lamivudine and tenofovir + didanosine, in patients with HIV infection and sustained viral suppression]. / Efectividad inmunológica de las combinaciones de análogos de nucleósidos/nucleótidos, tenofovir + lamivudina, didanosina + lamivudina y tenofovir + didanosina, en pacientes con infección por el VIH y supresión virológica mantenida.

BACKGROUND: Several recent studies have shown that the combination of ddI plus TDF can produce an unexpected drop in CD4 cell counts, even after correcting the ddI dose. OBJECTIVE: Comparative study of the immunological effectiveness of various once-daily NRTI backbones (ddI plus TDF, ddI plus 3TC or TDF plus 3TC) in antiretroviral-experienced HIV-infected patients achieving viral suppression (PCR, HIV-RNA < 50 copies/microl). METHODS: Prospective cohort study of 48 weeks' duration following viral load suppression with any of the NRTI combinations studied. The main outcome variable was the increase in CD4+ lymphocyte count from the time that viral load was undetectable or treatment was changed for simplification or toxicity (baseline) up to 48 weeks of follow-up. Differences between the assigned therapies were compared. The variables included in analysis were age, sex, risk group, HCV infection, clinical categories of HIV (CDC criteria), lowest CD4 cell count, reason for change of NRTI backbone, type of antiretroviral treatment (PI, NNRTI, or 3 NRTI) and duration of suppressed viral load. RESULTS. Regimens including ddI plus TDF showed significant decreases in CD4 cell counts with adjustments by type of HAART, reason for change, and duration of suppressed viral load. In patients treated with TDF + 3TC, CD4 count increased by 160 cel/microl (95% CI, 53-266) more than in patients treated with TDF + ddI; and in patients receiving ddI + 3TC, CD4+ count increased by 138 cel/microl (95% CI, 25-266) more than in patients receiving TDF + ddI. CONCLUSIONS: The ddI plus TDF backbone seems unadvisable because of the lower associated CD4 cell counts, and because it is poorer than the other options from the immunological standpoint.

Efectividad inmunologica de las combinaciones de analogos de nucleosidos / nucleotidos, tenofovir + lamivudina, didanosina + lamivudina y tenofovir + didanosina, en pacientes con infeccion por el VIH y supresion virologica mantenida / Immunological effectiveness of the nucleoside / nucleotide analog combinations, tenofovir + lamivudine, didanosine + lamivudine and tenofovir + didanosine, in patients with HIV infection and sustained viral suppression

Antecedentes. Recientemente, se ha comunicado en varios artículos que la combinación tenofovir (TDF) y didanosina (ddI) puede tener efecto paradójico en la respuesta inmunológica, incluso tras el ajuste de dosis de ddI. Objetivo. El objetivo de este trabajo es comparar en pacientes infectados por el virus de la inmunodeficiencia humana (VIH), con supresión virológica (reacción en cadena de la polimerasa [PCR] ARN-VIH < 50 copias/ìl), la efectividad inmunológica de ddI + TDF frente a ddI + lamivudina (3TC) o TDF + 3TC. Métodos. Estudio de cohortes prospectivo de 48 semanas de duración tras supresión virológica con cualquiera de las combinaciones de inhibidores de transcriptasa inversa nucleósidos (NRTI) del estudio. La variable principal de evaluación fue el incremento de la cifra de linfocitos CD4 desde el momento en que el paciente tiene una carga viral indetectable o desde el momento del cambio por simplificación o toxicidad (visita basal) hasta las 48 semanas. Introdujimos como variables de ajuste para dicho análisis la edad, el sexo, el grupo de riesgo, la infección por virus de la hepatitis C (VHC), el grupo de clasificación del Center for Disease Control and Prevention (CDC), recuento delinfocitos CD4+ nadir, motivos del cambio, el tipo de tratamiento antirretroviral (inhibidor de proteasa [IP], inhibidor de transcriptasa inversa no nucleósido [NNRTI] o combinación de inhibidores de transcriptasa inversa nucleósidos [3 NRTI]) y tiempo con carga viral indetectable. Resultados. Los regímenes que incluyeron TDF + ddI mostraron una reducción del recuento de CD4+. Ajustando por el tipo de tratamiento antirretroviral de gran actividad (TARGA), por los motivos del cambio, y por el tiempo con carga viral indetectable, en los pacientes que recibieron TDF + 3TC la cifra de linfocitos CD4 aumentó en 160 cél./ìl (intervalo de confianza del 95% [IC 95%]: 53-266) más que en los pacientes que recibieron TDF + ddI y que los pacientes que recibieron ddI + 3TC aumentaron 138 cél./ìl (IC 95%: 25-266) más que los que recibieron TDF + ddI. Conclusiones. La combinación ddI + TDF no es aconsejable, no sólo porque puede producir descenso del recuento de linfocitos CD4+, sino porque desde el punto de vista inmunológico es peor que las otras combinaciones (AU)

Background. Several recent studies have shown that the combination of ddI plus TDF can produce an unexpected drop in CD4 cell counts, even after correcting the ddI dose. Objective. Comparative study of the immunological effectiveness of various once-daily NRTI backbones (ddI plus TDF, ddI plus 3TC or TDF plus 3TC) in antiretroviral-experienced HIV-infected patients achieving viral suppression (PCR, HIV-RNA < 50 copies/ìl). Methods. Prospective cohort study of 48 weeks' duration following viral load suppression with any of the NRTI combinations studied. The main outcome variable was the increase in CD4+ lymphocyte count from the time that viral load was undetectable or treatment was changed for simplification or toxicity (baseline) up to 48 weeks of follow-up. Differences between the assigned therapies were compared. The variables included in analysis were age, sex, risk group, HCV infection, clinical categories of HIV (CDC criteria), lowest CD4 cell count, reason for change of NRTI backbone, type of antiretroviral treatment (PI, NNRTI, or 3 NRTI) and duration of suppressed viral load. Results. Regimens including ddI plus TDF showed significant decreases in CD4 cell counts with adjustments by type of HAART, reason for change, and duration of suppressed viral load. In patients treated with TDF + 3TC, CD4 count increased by 160 cel/ìl (95% CI, 53-266) more than in patients treated with TDF + ddI; and in patients receiving ddI + 3TC, CD4+ count increased by 138 cel/ìl (95% CI, 25-266) more than in patients receiving TDF + ddI. Conclusions. The ddI plus TDF backbone seems unadvisable because of the lower associated CD4 cell counts, and because it is poorer than the other options from the immunological standpoint (AU)