RESUMEN
We hypothesized that CD4(+)CD25(hi)FoxP3(+) regulatory T cells (Tregs) could be involved in the high immune activation existing in patients with low-level CD4 T-cell repopulation under suppressive high active antiretroviral therapy (hereafter, "LLR patients"). Sixteen LLR patients, 18 human immunodeficiency virus (HIV)-infected controls (hereafter, "HIV controls"), and 16 healthy subjects were included. The frequency of CD4(+)CD25(hi)FoxP3(+) and HIV-specific Treg suppressive function were assessed. Relationships between Treg and CD4/CD8 activation (HLA-DR/CD38) and the frequency of naive CD4 T-cells were assessed. Low-level patients showed a higher Treg frequency but reduced HIV-specific immunosuppressive functions than HIV controls. Whereas in healthy subjects a strong negative correlation between Tregs and activated CD8 T cells emerged (r = -0.75, P < .001), it appeared disrupted in both HIV-infected groups (r = -0.06 and P = .83 for LLR patients; r = -0.11 and P = .68 for and HIV controls). Nevertheless, in LLR patients, Tregs negatively correlated with naive CD4 T cells (r = -0.60, P = .01), whereas there was no such correlation in HIV controls (r = -0.19, P = .46) or healthy subjects (r = -0.10, P = .73). Remarkably, a higher ratio of Tregs to naive CD4 T cells was observed in LLR patients than in HIV controls (P = .001) and healthy subjects (P < .001). We conclude that LLR patients have important alterations in immunoregulation involving CD4(+)CD25(hi)FoxP3(+) Tregs. In this scenario, the role of Tregs seems to be more related to the control of the naive CD4 T-cell homeostatic proliferation, rather than to the immune activation.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/inmunología , VIH-1/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Antígenos CD4/metabolismo , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Antígeno CTLA-4/metabolismo , Estudios de Casos y Controles , Proliferación Celular/efectos de los fármacos , Estudios de Cohortes , Estudios Transversales , Femenino , Factores de Transcripción Forkhead/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Proteína Relacionada con TNFR Inducida por Glucocorticoide/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Inmunofenotipificación , Interleucina-2/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Activación de Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , España , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismoRESUMEN
Fundamento y objetivo: Describir las características de pacientes adultos con infección por el virus de la inmunodeficiencia humana (VIH) según su edad al momento de la inclusión en la Cohorte de la Red de Investigación en Sida (CoRIS). Pacientes y métodos: Análisis de una cohorte abierta, prospectiva, multicéntrica de adultos con infección por el VIH sin tratamiento antirretroviral previo, atendidos por primera vez entre enero de 2004 y noviembre de 2008, en 28 hospitales españoles (CoRIS). Se analizaron sus características en la primera visita y la distribución de las enfermedades definitorias de sida (EDS) a lo largo de la vida, según la edad al momento de la inclusión. El retraso diagnóstico se definió como pacientes con diagnóstico de sida o cifra de CD4+ inferior a 200 cel/μl durante el año posterior al diagnóstico de la infección por el VIH. Resultados: Participaron 4.418 personas; el 30,4% con 30 años o menos, el 60,6% de entre 31 y 50 años y el 8,9% de mayores de 50 años. El 31,6% de los pacientes eran inmigrantes (el 44,1% entre los jóvenes), el 79,6% correspondía a transmisión sexual y el 15,2% tenía diagnóstico de sida en la primera visita (el 28,1% entre los mayores de 50 años). El 34,6% de los pacientes tenía retraso diagnóstico (el 53,3% en los mayores de 50 años). La distribución de las EDS varió con la edad: las tuberculosis son más frecuentes en jóvenes y la neumonía por Pneumocystis jiroveci, la leucoencefalopatía multifocal progresiva, la encefalopatía por VIH, la neumonía recurrente y el linfoma cerebral primario son más frecuentes en los mayores. Conclusiones: Las características inmunológicas y las EDS varían con la edad. El porcentaje de personas con retraso diagnóstico es inaceptablemente alto, lo que indica que deben diseñarse intervenciones dirigidas a efectuar un diagnóstico más precoz (AU)
Background and objective: To describe the characteristics of HIV infected adults according to their age at recruitment in CoRIS. Patients and methods: Analysis of an open, prospective, multicentric cohort of HIV+ adults without previous antiretroviral treatment, attended for the first time from January/2004 to November/2008, in 28 Spanish hospitals (CoRIS). We analyzed their characteristics at recruitment and the distribution of AIDS defining illnesses (ADI) prior to cohort entry and during follow up, according to their age at recruitment. Delayed diagnosis was defined as a patient with AIDS diagnosis and/or CD4+ cell count lower than 200 cells/μl within the first year after HIV diagnosis. Results: Of 4,418 patients included, 30.4% were <=30 years old, 60.6% between 31 and 50 and 8.9% older than 50 at cohort entry; 31.6% of patients were immigrants (44.1% in the youngest group), 79.6% had been sexually transmitted and 15.2% had an AIDS diagnosis at cohort entry (28.1% between those older than 50). In 34.6% of cases there was a late diagnosis (53.3% in the oldest group). The ADIs varied according to age; tuberculosis was more frequent in the youngest. Pneumocystis jiroveci pneumonia, progressive multifocal leukoencephalopathy, HIV related encephalopathy, recurrent pneumonia and primary lymphoma of brain were more frequent among the oldest. Conclusions: The immunological characteristics and the distribution of ADIs varied according to age. The proportion of late diagnosis was unacceptably high, suggesting the need of specific interventions designed to promote earlier diagnosis (AU)
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Infecciones por VIH/prevención & control , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Encuestas Epidemiológicas , Estudios Prospectivos , Factores de Edad , Factores Socioeconómicos , Factores de Tiempo , España/epidemiología , Estudios de CohortesRESUMEN
BACKGROUND AND OBJECTIVE: To describe the characteristics of HIV infected adults according to their age at recruitment in CoRIS. PATIENTS AND METHODS: Analysis of an open, prospective, multicentric cohort of HIV+ adults without previous antiretroviral treatment, attended for the first time from January/2004 to November/2008, in 28 Spanish hospitals (CoRIS). We analyzed their characteristics at recruitment and the distribution of AIDS defining illnesses (ADI) prior to cohort entry and during follow up, according to their age at recruitment. Delayed diagnosis was defined as a patient with AIDS diagnosis and/or CD4+ cell count lower than 200 cells/microl within the first year after HIV diagnosis. RESULTS: Of 4,418 patients included, 30.4% were < or =30 years old, 60.6% between 31 and 50 and 8.9% older than 50 at cohort entry; 31.6% of patients were immigrants (44.1% in the youngest group), 79.6% had been sexually transmitted and 15.2% had an AIDS diagnosis at cohort entry (28.1% between those older than 50). In 34.6% of cases there was a late diagnosis (53.3% in the oldest group). The ADIs varied according to age; tuberculosis was more frequent in the youngest. Pneumocystis jiroveci pneumonia, progressive multifocal leukoencephalopathy, HIV related encephalopathy, recurrent pneumonia and primary lymphoma of brain were more frequent among the oldest. CONCLUSIONS: The immunological characteristics and the distribution of ADIs varied according to age. The proportion of late diagnosis was unacceptably high, suggesting the need of specific interventions designed to promote earlier diagnosis.