Immune reconstitution in HIV-infected children on antiretroviral therapy

La infección VIH conduce a una depleción severa de células TCD4+, alteraciones del fenotipo de las subpoblaciones linfocitarias,disminución de la función tímica que a su vez produce un deterioro progresivo de la función inmunitaria. La introducción de la terapia antirretroviral de gran actividad (TARGA) ha disminuido la progresión clínica, suprime la carga viral (CV) e incrementa las células TCD4+ en pacientes infectados por el VIH. Sin embargo, los niños en TARGA suelen tener CV más elevada y peor respuesta virológica que en adultos. No obstante, en los niños infectados por el VIH con bajos valores de células T CD4+, la TARGA produce un aumento consistente de células T CD4+ y de los llamados T-cell rearrangement excision circles (TRECs). Estos resultados indican que la recuperación de la función tímica juega un papel clave en la reconstitución inmunitaria de los niños con VIH. Entre las citocinas identificadas como posibles reguladoras de la timopoyesis, la IL-7 puede jugar un papel esencial.La IL-7 participa en la diferenciación de los timocitos a células Tvirgen maduras en el timo que posteriormente salen a sangre periférica.Varios trabajos han demostrado la correlación inversa entre niveles plasmáticos de IL-7 y las células T CD4+. Por consiguiente, el aumento de IL-7 se ha propuesto como una respuesta homeostática a la depleción de células T CD4+. También se ha comprobado una inhibición de la timopoyesis por cepas virales X4 independientemente de la edad debido a la capacidad de las cepas X4 de infectar a los timocitos.Sin embargo se ha demostrado que la TARGA disminuye el número de aislados virales con fenotipo X4 en los niños con VIH. Enconclusión, la TARGA ha mostrado ser eficaz disminuyendo la CV y aumentando el número de células T CD4+, proceso que depende de la función tímica y estaría regulado por IL-7 (AU)

HIV-infection leads to a severe depletion of CD4+ T-cells, phenotypicalterations of T-cell subsets and a decline in thymic function,which in turn produces a progressive impairment of the immune function.The introduction of highly active antiretroviral therapy (HAART)decreased mortality rates in HIV-infection, and proved to be effective in suppressing plasma viral loads (VL) and increasing CD4+ T-cellcounts in children. However, children receiving treatment usually have higher VL and lower virological response rates than adults. But after severe depletion of T-cells, HAART results in a consistent increase in CD4+ T-cell counts and T-cell rearrangement excision circles(TREC) levels in young HIV-infected patients. These findings indicate that recovery of thymic function is a pivotal event in immunere constitution. Among the cytokines and hormones identified as possible regulators of thymopoiesis, IL-7 may play an essential role. IL-7 has been shown to take part in the differentiation of thymocytes intomature T-cells that will leave the thymus and move to the periphery.Several studies have reported higher plasma IL-7 levels in HIVpatients, which inversely correlate with CD4+ T-cell counts. The increaseof IL-7 has therefore been suggested to be a homeostatic response to T-cell depletion. Furthermore, thymopoiesis is inhibited by X4strains, independent of the age of the infected person. This could be due to the capacity of X4 strains to infect thymocytes. However,HAART produces a decrease in the amount of X4 strain isolates inHIV-infected children. In conclusion, HAART has shown to be effective in decreasing VL and increasing the immune function of CD4+ Tcells. This process is dependent on the function of the thymus as well as the homeostatic mechanisms of IL-7 (AU)

Immune reconstitution in HIV-infected children on antiretroviral therapy

La infección VIH conduce a una depleción severa de células TCD4+, alteraciones del fenotipo de las subpoblaciones linfocitarias,disminución de la función tímica que a su vez produce un deterioroprogresivo de la función inmunitaria. La introducción de la terapiaantirretroviral de gran actividad (TARGA) ha disminuido la progresiónclínica, suprime la carga viral (CV) e incrementa las células TCD4+ en pacientes infectados por el VIH. Sin embargo, los niños enTARGA suelen tener CV más elevada y peor respuesta virológica queen adultos. No obstante, en los niños infectados por el VIH con bajosvalores de células T CD4+, la TARGA produce un aumento consistentede células T CD4+ y de los llamados T-cell rearrangement excisioncircles (TRECs). Estos resultados indican que la recuperación dela función tímica juega un papel clave en la reconstitución inmunitariade los niños con VIH. Entre las citocinas identificadas como posiblesreguladoras de la timopoyesis, la IL-7 puede jugar un papel esencial.La IL-7 participa en la diferenciación de los timocitos a células Tvirgen maduras en el timo que posteriormente salen a sangre periférica.Varios trabajos han demostrado la correlación inversa entre nivelesplasmáticos de IL-7 y las células T CD4+. Por consiguiente, elaumento de IL-7 se ha propuesto como una respuesta homeostáticaa la depleción de células T CD4+. También se ha comprobado unainhibición de la timopoyesis por cepas virales X4 independientementede la edad debido a la capacidad de las cepas X4 de infectar a los timocitos.Sin embargo se ha demostrado que la TARGA disminuye elnúmero de aislados virales con fenotipo X4 en los niños con VIH. Enconclusión, la TARGA ha mostrado ser eficaz disminuyendo la CV yaumentando el número de células T CD4+, proceso que depende dela función tímica y estaría regulado por IL-7

HIV-infection leads to a severe depletion of CD4+ T-cells, phenotypicalterations of T-cell subsets and a decline in thymic function,which in turn produces a progressive impairment of the immune function.The introduction of highly active antiretroviral therapy (HAART)decreased mortality rates in HIV-infection, and proved to be effectivein suppressing plasma viral loads (VL) and increasing CD4+ T-cellcounts in children. However, children receiving treatment usuallyhave higher VL and lower virological response rates than adults. Butafter severe depletion of T-cells, HAART results in a consistent increasein CD4+ T-cell counts and T-cell rearrangement excision circles(TREC) levels in young HIV-infected patients. These findings indicatethat recovery of thymic function is a pivotal event in immunereconstitution. Among the cytokines and hormones identified as possibleregulators of thymopoiesis, IL-7 may play an essential role. IL-7 has been shown to take part in the differentiation of thymocytes intomature T-cells that will leave the thymus and move to the periphery.Several studies have reported higher plasma IL-7 levels in HIVpatients, which inversely correlate with CD4+ T-cell counts. The increaseof IL-7 has therefore been suggested to be a homeostatic responseto T-cell depletion. Furthermore, thymopoiesis is inhibited by X4strains, independent of the age of the infected person. This could bedue to the capacity of X4 strains to infect thymocytes. However,HAART produces a decrease in the amount of X4 strain isolates inHIV-infected children. In conclusion, HAART has shown to be effectivein decreasing VL and increasing the immune function of CD4+ Tcells. This process is dependent on the function of the thymus as wellas the homeostatic mechanisms of IL-7

[Dissociated cholestasis in patients with HIV-1 infection, Prevalence and diagnostic value of liver biopsy]. / Colestasis disociada en pacientes infectados por el VIH-1. Prevalencia y valor diagnóstico de la biopsia hepática.

HIV-1 infected patients frequently develop opportunistic diseases involving the liver, particularly individuals with AIDS. Nevertheless, the role of liver biopsy (LB) in these patients is controversial. The prevalence of AC in seropositive subjects and the value of LB in patients with AC was investigated. The prevalence of AC in all outpatients attended at our Unit for a three month period was 2/119 (1.6%), whereas it was 20/66 (30.3%) for inpatients for a nine month period. LB was proposed to all patients with AC but not to those with a Karnofski index < 50 and those with an ethanol intake > 80 g per day. LB was performed in 16 patients, four were excluded, and 2 refused the procedure. Among symptomatic patients, LB: a) confirmed a previous diagnosis in six patients (40%); b) showed findings of nonspecific cholangitis in four cases (27%), and c) disclosed a previously unsuspected or unconfirmed disease in five patients (33%). LB is an useful diagnostic tool for the diagnosis of seropositive patients with AC, although a previous opportunistic event may account for symptoms and the corresponding enzymatic patterns.

[Acute human immunodeficiency virus infection associated with facial diplegia]. / Infección aguda por el virus de la inmunodeficiencia humana asociada a diplejia facial.

We describe the case of a 21-year-old parenterally drug-addict man, who presented an acute and self-limited disease, temporarily associated to seroconversion against the human immunodeficiency virus. During his evolution, the patient developed aseptic meningitis and facial diplegia. Two lymphatic ganglions were histopathologically and sequentially studied during the third and sixth week of the disease, showing an intense follicular depletion in the first sample, which reverted towards a pattern of follicular hyperplasia in the second one.

[Epidemiological study of healthy carriers of Australia antigen. Analysis of contagiousness, and mechanism of spread of the infection (author's transl)]. / Estudio epidemiológico de los portadores sanos de antíaeno Australia. Análisis de su infecto-contagiosidad y mecanismo de aparición de nuevos casos.

Epidemiological studies in healthy carriers of HB Ag show variable results that might depend on the geographical area, ethnic group, and socio-economic level analyzed. For that reason an study was undertaken in the Spanish population with the purpose of analysing contagiousness of healthy carriers and mechanism of spread of the infection. The incidence of HB Ag and HB Ab was determined by radioimmunoassay in 211 relatives of 76 healthy carriers; all members of the family could be studied in 51 cases. The results were compared to those of a sizeable sample of the normal population. The overall incidence of HB Ag (13.1 %), and of HB Ab (18.9 %) in the probands was significantly higher than in the normal population (0.8 %, and 9 %, respectively). The distribution of new cases of HB Ag positivity in the 51 families in which the members could be studied demonstrated a significantly higher frequency in children of a carrier mother (28.9 %) than in those of a carrier father (10.8 %). In conclusion, the contagiousness of healthy carriers for their families can not be disregarded. It is likely that the mechanism of spread of the infection depends on a multifactorial inheritance of the genetic alteration of the selective immunologic response to the HB Ag, compounded by environmental factors.

[Persistent and asymptomatic carriers of Australia antigen. A method for the evaluation of big series (author's transl)]. / Portadores persistentes y asintomáticos de antígeno Australia. Sistemática para la valoración de series amplias.

The existence of an increasing number of apparently healthy carriers of the HBsAg demands a specific assisting attitude which must be highly reliable without increasing health care expenses. With that purpose, 129 asymptomatic carriers without prior history of jaundice and/or alcohol abuse were studied. The following discriminant criteria were used: hepatomegaly, other physical evidence of liver disease, hypertransaminasemia, and sulfobromophthalein retention. The carrier was defined as healthy after two consecutive examinations disclosing no abnormalities at intervals of six months, which occurred in 108 patients (84 %). No patient underwent liver biopsy, but the examination was still normal after two years in all cases. The presence of one or more abnormal findings was an indication for liver biopsy in 21 patients (16 %), and the procedure was accepted by 11 (52 %). The efficiency of the selection method was evaluated according to the histologic findings. The most useful criteria were hypertransaminasemia and sulfobromophthalein retention, in this order.