Avaliação longitudinal do perfil fenotípico de leucócitos e análise do gene codificador de CCR5 do sangue periférico de crianças infectadas verticalmente pelo HIV-1 que progridem lentamente na infecção

Abstract

Objectives: The mechanisms involved in the slow progression of HIV-l infection in children with natural control of infection, have not been sufficiently characterized. In this study, children vertically infected by HIV-I showing distinct patterns of evolution were longitudinally followed for three years and assessed for phenotypic profile of circulating leukocytes and the presence of mutations in the gene encoding CCR5. Design: A longitudinal study conducted in 28 children vertically infected with HIV,over six years of age, distributed into two groups: Group NT (untreated: no indication for antiretroviral therapy, CD4 count 20% and / or 500 cells/mm3 and viral load <25,000 copies) and Group T: (Treated: antiretroviral therapy initiated before six years of age). Cellular immunophenotyping was perfomied by flow cytometry to assess cellactivation, the expression of CCR5 and subpopulations of NK cells, the viral load determination by b-DNA technique and evaluation of the gene encoding CCR5 was made by PCR. Results: In follow-up period, it was shown that children of both groups remained with stable levels of CD4+ and CD8+ T cells, as well as viral load. Cellular activation status, measured by analyzing the expression of CD38 and HLA-DR on CD4+and CD8+ T cells, was similar in both groups and remained throughout the follow-up, except for the observed increase in expression of HLA-DR on CD4+ in T group. Regarding the subpopulations of NK cells, we observed that children from NT group had a lower proportion of NK cells subpopulation with cytotoxic activity and this difference was maintained during the study. In group T, an increase in the percentage of NK cells CD3`CDI6`CD56b"gh° among the evaluated times was noted, showing good evolution of the infection. In relation to CCR5 expression in CD4+ cells, there was no difference between both groups. In the genetic evaluation, only one individual presented heterozygous profile for deletion of CCR5. Surprisingly this child had worsening of infection during the study period and was excluded from the NT group. Conclusions:The profile of cell activation was not related to the clinical profile, since itremained similar in both groups. The predominance of NK cells associated with lower cytotoxic capacity proved to be a stable parameter, allowing the distinction between the two groups of patients throughout the study period. Still, the stability observed in the evolution of children with slow progression could not be attributed to low expression of CCR5 on CD4+ T cells, since there was no difference in the expression of this receptor between groups and no child who remained in the NT group showed deletion of CCR5.