HIV-1 p24 and CD4+ T cell count during boosted protease-inhibitor monotherapy in HIV-infected patients / P24 y recuentos de CD4 durante el tratamiento con inhibidores de la proteasa potenciados en monoterapia

BACKGROUND: Plasma HIV p24 is considered a significant predictor of CD4+ T cell decline and progression to AIDS in HIV-infected patients. We evaluated the p24 levels in patients on triple therapy and after switching to ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv), as well as the relationships with virological and immunological evolution. MATERIALS AND METHODS: Plasma samples from patients participating in two studies of simplification to mtPI/rtv were analysed for presence of p24, using a boosted enzyme-linked immunosorbent assay specific for mature p24. Only patients with available samples at baseline (on triple therapy) and during a follow-up of at least 12 months after switching to mtPI/rtv were included. RESULTS: A total of 233 samples from 51 patients were analysed. After switching to mtPI/rtv and a median follow-up of 24 months, 14 patients maintained continuous undetectable viraemia, and 37 patients experienced a total of 49 transient viraemic episodes. Unexpectedly, the evolutionary p24 patterns were uniform for most patients, both before and after switching to mtPI/rtv, independently of the virological behaviour, fitting into one of three categories: persistent undetectable p24 levels, positive p24, matching only with the viraemic episodes, and persistent detectable p24 levels. The last group showed lower CD4+ T cell counts and percentages, as well as lower CD4+/CD8+ T cell ratios after 12 and 24 months of follow up. CONCLUSION: Treatment simplification to mtPI/rtv does not influence the behaviour of p24 in plasma. Patients with continuous positive p24, despite undetectable viraemia, showed worse immunological evolution

INTRODUCCIÓN: El antígeno p24 se considera un buen predictor de caída de los recuentos de linfocitos T CD4+ y de progresión a sida en pacientes infectados por el VIH. En este estudio hemos evaluado la presencia de p24 en plasma y su relación con la evolución virológica e inmunológica durante la monoterapia con inhibidores de la proteasa potenciados (mtPI/rtv). MATERIAL Y MÉTODOS: Se analizaron muestras de pacientes que participaron en 2 estudios de simplificación con mtPI/rtv. Las concentraciones de p24 se midieron mediante un ELISA potenciado específico para p24 madura. Solo se incluyeron los pacientes con muestras disponibles basalmente (en triple terapia) y durante≥12 meses de seguimiento con mtPI/rtv. RESULTADOS: Se analizaron un total de 233 muestras de 51 pacientes. Tras la simplificación y una mediana de seguimiento de 24 meses, 14 pacientes mantuvieron una viremia indetectable de forma continuada, mientras que se observaron 49 episodios de viremia transitoria en los 37 restantes. Las determinaciones de p24 fueron estables en la mayoría de los pacientes, tanto antes como después del cambio a mtIP/rtv, independientemente del comportamiento virológico, incluyéndose en una de las siguientes categorías: p24 indetectable persistentemente, p24 positiva coincidiendo solo con los episodios de viremia transitoria, y p24 detectable en todas las determinaciones. Este último grupo mostró recuentos y porcentajes de linfocitos T CD4+ más bajos, así como cocientes CD4+/CD8+ inferiores tras 12 y 24 meses de seguimiento. CONCLUSIÓN: La simplificación a mtPI/r no modifica el comportamiento de la p24 en plasma. Los pacientes con detección persistente de p24 en plasma a pesar de una viremia indetectable muestran una peor evolución inmunológica

HIV-1 p24 and CD4+ T cell count during boosted protease-inhibitor monotherapy in HIV-infected patients.

BACKGROUND: Plasma HIV p24 is considered a significant predictor of CD4+ T cell decline and progression to AIDS in HIV-infected patients. We evaluated the p24 levels in patients on triple therapy and after switching to ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv), as well as the relationships with virological and immunological evolution. MATERIALS AND METHODS: Plasma samples from patients participating in two studies of simplification to mtPI/rtv were analysed for presence of p24, using a boosted enzyme-linked immunosorbent assay specific for mature p24. Only patients with available samples at baseline (on triple therapy) and during a follow-up of at least 12 months after switching to mtPI/rtv were included. RESULTS: A total of 233 samples from 51 patients were analysed. After switching to mtPI/rtv and a median follow-up of 24 months, 14 patients maintained continuous undetectable viraemia, and 37 patients experienced a total of 49 transient viraemic episodes. Unexpectedly, the evolutionary p24 patterns were uniform for most patients, both before and after switching to mtPI/rtv, independently of the virological behaviour, fitting into one of three categories: persistent undetectable p24 levels, positive p24, matching only with the viraemic episodes, and persistent detectable p24 levels. The last group showed lower CD4+ T cell counts and percentages, as well as lower CD4+/CD8+ T cell ratios after 12 and 24 months of follow up. CONCLUSION: Treatment simplification to mtPI/rtv does not influence the behaviour of p24 in plasma. Patients with continuous positive p24, despite undetectable viraemia, showed worse immunological evolution.

Prevention of cytomegalovirus disease using pre-emptive treatment after solid organ transplant in patients at high risk for cytomegalovirus infection.

BACKGROUND: The use of pre-emptive or prophylactic treatment to control cytomegalovirus (CMV) replication after solid organ transplant (SOT) remains controversial. The aim of this study was to evaluate whether administration of pre-emptive treatment to control viral replication guided by a highly sensitive diagnostic tool is an effective approach for preventing CMV disease, even in high-risk transplant recipients. METHODS: Plasma samples from eight SOT patients were tested using antigenaemia and real-time PCR (RT-PCR) assays. Pre-emptive treatment was administered guided by RT-PCR when viral load values were >1,000 copies/ml. RESULTS: All patients developed episodes of CMV infection, but none of them developed CMV disease or indirect effects. No patient in this study died or experienced graft rejection. Treatment was needed in 10 replication episodes. At the end of treatment, four had undetectable levels and the other six were cleared 3 weeks later. In 42.6% of tested samples RT-PCR was more sensitive for detecting viral infection. CONCLUSIONS: Pre-emptive monitoring of SOT patients at high risk for CMV infection protected patients from developing CMV disease during the first 6 months after transplant. The use of this sensitive method for guiding pre-emptive treatment diminished viral load early enough that it did not have consequences for patient health.