HIV-1-infected children on HAART: immunologic features of three different levels of viral suppression.

HIV-1-infected children show changes of blood lymphocyte subpopulations. We have, therefore, investigated how highly active anti-retroviral therapy (ART) alter these subsets. Blood samples were taken from 41 HIV-1-infected children on ART who were divided into groups showing good, partial and poor responses to ART on the basis of viral load (VL) measurement in blood. The observations were compared to those seen in 20 uninfected children. The samples were studied using 4-color flow cytometry for "naïve", central memory and effector memory cells as well as for CD38 expression as the sign of activation within both the CD4+ and the CD8+ T cell populations. HIV-1 infected children were also evaluated for the presence and the titers of antibodies induced by vaccination against childhood infections in our patients while on HAART. Lymphocyte counts were lower in the "poor" viral load responding (VLR) group when compared with partial and good VLRs. Poor VLRs had lower total and naïve CD4+ T cell counts. HIV-1-infected children from all three groups had high CD8+ T cell counts. Central memory CD4+ and CD8+ T cell percentages were particularly low in the poor VLR group while in the poor VLR group the percentages of effector memory CD4+ and CD8+ T cells were higher when compared with the control group. Higher cellular activation of CD8+ T cells was observed in HIV-1-infected children, particularly when analyzed for the intensity of CD38 expression in the poor VLR group. CD5 expression on B cells was higher among all HIV-1-infected children. Antibodies to tetanus, diphtheria, measles, rubella, and hepatitis B were present in a large proportion of children but the titers were similarly low for all three groups of HIV-infected children. Children with different levels of viral response to HAART present immune phenotype characteristics that tend to place the children with partial and good virological responses into the same group. These children are still moderately deficient in their immune responses but show better recovery than seen with children in the poor VLR group. These observations indicate that the proportions of central memory cells among the CD4+ T cells and the intensity of the expression of CD38 activation antigen on CD8+ T cells provide more informative parameters for monitoring children on HAART than the absolute numbers of CD4+ and CD8+ T cells alone.

Zaccarelli-Filho CA ，Ono E ，Machado DM ，Brunialti M ，Succi RC ，Salomão R ，Kallás EG ，de Moraes-Pinto MI ... -  《CYTOMETRY PART B-CLINICAL CYTOMETRY》

Relationship between CD38 expression on peripheral blood T-cells and monocytes, and response to antiretroviral therapy: a one-year longitudinal study of a cohort of chronically infected ART-naive HIV-1+ patients.

HIV-1 infection has been associated with high expression of CD38 on peripheral blood (PB) CD8+ and CD4+ T-cells, which has been related with poor prognosis in untreated HIV-1+ patients. In turn, CD38 expression on PB monocytes from HIV-1+ individuals and its behavior after starting antiretroviral therapy (ART) have been poorly studied. CD38 expression on PB CD8+ and CD4+ T-lymphocytes and monocytes was prospectively analyzed in 30 ART-naive HIV-1+ patients, using a quantitative multiparameter flow cytometry approach. Patients were tested prior to therapy, and at weeks +2, +4, +8, +12, and +52 after ART. Prior to ART, CD38 expression was significantly increased on PB CD8+ and CD4+ T-cells and monocytes; despite a significant decrease after ART, CD38 expression remained abnormally high on PB CD8+ T-cells and monocytes, even after one year of therapy, in the absence of detectable plasma viral load. The ART-induced early changes on CD38 expression by PB T-cells and monocytes differed among the cell subsets analyzed and patient groups, probably reflecting an interaction between the direct effects of therapy and a redistribution of the PB compartments of T-cells and monocytes. Hierarchical clustering analysis showed that the overall pattern of changes in CD38 expression observed early after starting ART was predictive of a better response to therapy, not only for PB CD8+ T-cells, but also for CD4+ T-cells and monocytes. Accordingly, those HIV-1+ patients, who experienced a more pronounced increase in CD38 expression on both PB CD4+ T-cells and monocytes after 2 weeks of ART, showed a more rapid viral clearance, which might reflect decreased HIV-1 replication in lymph nodes and other tissues, and a partial restoration of hematopoiesis. Combined quantitative measurement of CD38 expression on PB monocytes, and CD8+ and CD4+ T-cells is a more useful tool for monitoring HIV-1+ patients under ART, rather than quantitation of CD38 expression on PB CD8+ T-lymphocytes alone.

Almeida M ，Cordero M ，Almeida J ，Orfao A ... -  《CYTOMETRY PART B-CLINICAL CYTOMETRY》

Immunologic features of HIV-1-infected women on HAART at delivery.

The conjoint effect of HIV infection and pregnancy on the immune system of women submitted to the prophylactic antiretroviral therapy presently recommended is still poorly understood. We evaluated 44 HIV-infected women (HIV) and 45 HIV-negative women (CT) at parturition and we compared them to 20 healthy nonpregnant women (NP). Immunophenotyping of lymphocytes was done by four-color flow cytometry. All HIV-infected women received HAART during pregnancy and 56.8% had viral load <50 copies/mL at delivery. CD4+T cells/mm(3) were lower in HIV (447) than CT (593) and NP (738) (P < 0.05). CD8+T cells/mm(3) were higher in HIV (799) than CT (384) and NP (395) (P < 0.05). NK cells/mm(3) were lower in HIV (146) than in CT (253) and NP (198) (P < 0.05). CD38 expression on CD4+T and on CD8+T cells was higher in HIV (CD4:12.1; CD8:14.9) than in CT(CD4:9.2; CD8:10.2) and NP(CD4:8.6; CD8:6.0) (P < 0.05). However, CD56 expression on CD8+T cells (a marker of cytolytic effector function) was lower in HIV(7%) than in CT(12%) and NP(9%) (P < 0.05). Even with low levels of viremia, HIV-infected women at delivery showed a different immunologic profile from both healthy non-HIV-infected women in the puerperium and nonpregnant women, with lower CD4+T and higher CD8+T cells, high levels of CD38 expression, but low CD56 expression on CD8+T cells and low NK cell numbers.

Ono E ，Dos Santos AM ，Machado DM ，Succi RC ，Amed AM ，Salomão R ，Kallás EG ，de Moraes-Pinto MI ... -  《-》

Presence of human immunodeficiency virus-1-specific CD4 and CD8 cellular immune responses in children with full or partial virus suppression.

Papasavvas E ，Sandberg JK ，Rutstein R ，Moore EC ，Mackiewicz A ，Thiel B ，Pistilli M ，June RR ，Jordan KA ，Gross R ，Maino VC ，Nixon DF ，Montaner LJ ... -  《JOURNAL OF INFECTIOUS DISEASES》

[T-cell subsets variation during clinical and immunological progression in vertically HIV-infected children].

Resino García S ，Bellón Cano JM ，Navarro Caspistegui J ，Gurbindo Gutiérrez D ，León Leal JA ，Muñoz-Fernández MA ... -  《MEDICINA-BUENOS AIRES》