Infección por Citomegalovirus en Receptores de Trasplante de Órgano Sólido y efecto terapéutico de la adquisición de respuesta inmune específica

Motivación: A pesar de las mejoras de tratamiento, la infección por CMV es la principal causa de morbimortalidad en los pacientes con  trasplante de órgano sólido (TOS) con una incidencia de enfermedad tardía (>3 meses post-trasplante) por CMV que varía entre 6-30% (1).  La respuesta inmune mediada por células T capaces de secretar IFN-gamma tras la estimulación con CMV constituye la principal defensa frente a la infección viral (2) y juega un papel crucial en el control de las infecciones post-trasplante. Los pacientes seronegativos para CMV que reciben un trasplante de un donante seropositivo (D+/R-), son considerados de alto riesgo de desarrollar infección por CMV tras el trasplante ya que no presentan inmunidad previa.  El tratamiento anticipado con ganciclovir frente a CMV iniciado cuando la carga viral  alcanza un umbral determinado (3), no está recomendado en pacientes de alto riesgo, los cuales reciben profilaxis continua durante 100 días post-trasplante. Nuestra hipótesis fue que la administración de tratamiento anticipado en pacientes D+/R- podría permitir la exposición controlada al CMV que promoviera el desarrollo de inmunidad específica.Métodos: Se incluyeron pacientes D+/R- y se recogieron muestras de seguimiento durante 18 meses tras el trasplante. Se determinó la carga viral de CMV por PCR en tiempo real. Para determinar la respuesta inmune de células T la sangre completa fue estimulada con péptidos específicos de CMV (pp65 y IE-1), se llevó a cabo la tinción con anticuerpos de moléculas de superficie (CD8, CD4, CD69), y citoquinas intracelulares implicadas en la respuesta celular (IL2,IL4 e IFN-g), y se análizó mediante citometría de flujo. Además se está determinando los títulos de anticuerpos neutralizantes para bloquear la infección de células epiteliales y fibroblastos.Resultados: Los 21 pacientes estudiados desarrollaron episodios de replicación con una mediana de 4 semanas tras el trasplante, y una respuesta inmune específica con una mediana de 12 semanas. La incidencia de los episodios de replicación estuvo inversamente relacionada con la adquisición de la respuesta inmune. Tras la adquisición de la respuesta inmune todos los episodios de replicación fueron aclarados sin necesidad de tratamiento, ninguno de ellos desarrolló enfermedad tardía por CMV ni episodios de rechazo.Conclusiones: El tratamiento anticipado es eficaz para prevenir la infección por CMV en paciente D+/R- y promueve la respuesta inmune específica protectora

No differences of immune activation and microbial translocation among HIV-infected children receiving combined antiretroviral therapy or protease inhibitor monotherapy.

This is a cross-sectional study of 15 aviremic chronic HIV-infected children revealing no differences in immune activation (IA; HLA-DRCD38 CD4 and CD8 T cells, and sCD14) and microbial translocation (MT; lipopolysaccharides (LPS) and 16S rDNA) among HIV-infected patients under combined antiretroviral treatment (cART; n = 10) or ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv; n = 5). In both cases, IA and MT were lower in healthy control children (n = 32). This observational study suggests that ritonavir boosted protease inhibitor monotherapy (mtPI/rtv) is not associated with an increased state of IA or MT as compared with children receiving cART

No Differences of Immune Activation and Microbial Translocation Among HIV-infected Children Receiving Combined Antiretroviral Therapy or Protease Inhibitor Monotherapy

This is a cross-sectional study of 15 aviremic chronic HIV-infected children revealing no differences in immune activation (IA; HLA-DRCD38 CD4 and CD8 T cells, and sCD14) and microbial translocation (MT; lipopolysaccharides (LPS) and 16S rDNA) among HIV-infected patients under combined antiretroviral treatment (cART; n = 10) or ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv; n = 5). In both cases, IA and MT were lower in healthy control children (n = 32). This observational study suggests that ritonavir boosted protease inhibitor monotherapy (mtPI/rtv) is not associated with an increased state of IA or MT as compared with children receiving cART

No differences of immune activation and microbial translocation among HIV-infected children receiving combined antiretroviral therapy or protease inhibitor monotherapy.

This is a cross-sectional study of 15 aviremic chronic HIV-infected children revealing no differences in immune activation (IA; HLA-DRCD38 CD4 and CD8 T cells, and sCD14) and microbial translocation (MT; lipopolysaccharides (LPS) and 16S rDNA) among HIV-infected patients under combined antiretroviral treatment (cART; n = 10) or ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv; n = 5). In both cases, IA and MT were lower in healthy control children (n = 32). This observational study suggests that ritonavir boosted protease inhibitor monotherapy (mtPI/rtv) is not associated with an increased state of IA or MT as compared with children receiving cART

Viral Kinetics in Semen With Different Antiretroviral Families in Treatment-Naive Human Immunodeficiency Virus-Infected Patients: A Randomized Trial

Background. There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of human immunodeficiency virus (HIV) RNA decay in semen.Objective. To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma (SP) of treatment-naive HIV-infected patients.Methods. Phase II, randomized, open-label study in which participants were randomized 1: 1: 1 to receive tenofovir-disoproxil fumarate (DF) plus emtricitabine, and either cobicistat-boosted elvitegravir (EVG(cobi)), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv). The primary endpoint was the proportion of participants with undetectable HIV-RNA in SP at week 12. HIV type 1 (HIV-1) RNA was measured in paired SP and blood plasma (BP) at baseline and after 1, 2, 4, 6, 8, 12, 18, and 24 weeks. Elvitegravir (EVG), RPV, and darunavir (DRV) concentrations were quantified by the liquid chromatography-tandem mass spectrometry method.Results. In SP, the HIV-RNA decay rate with RPV was as fast as with EVG(cobi); by week 12, all participants in the RPV and the EVG(cobi) groups reached an undetectable viral load but only 58.3% in the DRVrtv arm (P = .003). The highest SP/BP drug concentration ratio was for EVG (0.43), followed-up by RPV (0.19), and DRV (0.10). For both EVG and RPV, the SP concentrations exceeded >2-fold the protein binding-adjusted EC90 for wild-type HIV-1; for DRV, only 33.7% of the SP showed concentrations above the protein binding-adjusted EC90.Conclusions. In SP, both RPV and EVG(cobi), associated to tenofovir-DF and emtricitabine, behave similarly and achieve an undetectable viral load much faster than DRVrtv

Eradication of Hepatitis C Virus (HCV) Reduces Immune Activation, Microbial Translocation, and the HIV DNA Level in HIV/HCV-Coinfected Patients.

There are contradictory data about the influence that hepatitis C virus (HCV) has on immune activation and inflammation in patients coinfected with human immunodeficiency virus (HIV) and HCV. HIV/HCV-coinfected patients receiving antiretroviral treatment who achieved a sustained virological response with interferon-free regimens were consecutively enrolled in a prospective study. The following factors were assessed before, immediately after the end of, and 1 month after the end of therapy: expression of HLA-DR/CD38, PD-1, and CD57 on CD4+ and CD8+ T-cells; measurement of the total HIV DNA load in peripheral blood mononuclear cells; and determination of plasma levels of soluble CD14 (sCD14), lipopolysaccharide (LPS), 16S ribosomal DNA (rDNA), interleukin 6 (IL-6), D-dimers, and high-sensitivity C-reactive protein (hsCRP). Ninety-seven patients were consecutively included. At the end of therapy and 1 month later, there were significant reductions in the expression of HLA-DR and CD38 in CD4+ and CD8+ T cells, as well as levels of proviral HIV DNA, sCD14, LPS, 16S rDNA, and D-dimer (P HCV eradication in HIV/HCV-coinfected patients results in significant decreases in levels of immune activation markers, proviral HIV DNA load, microbial translocation markers, and D-dimers. These findings support the use of HCV treatment for all HIV/HCV-coinfected patients, even those with low-grade fibrosis