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Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1β levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown.

Background: We investigated immune activation, exhaustion markers and cytokine expression upon stimulation in adolescents with vertical HIV infection. Methods: Thirty adolescents receiving antiretroviral therapy (ART) for vertical HIV infection, including 12 with detectable viral load (HIV/DET), 18 with undetectable viral load (HIV/UND) and 30 control adolescents without HIV infection (CONTROL), were evaluated for immune activation and programmed cell death protein-1 expression by flow cytometry, and 21 cytokines by Luminex Multiple Analyte Profiling technology after in vitro peripheral blood phytohemagglutinin stimulation. Results: Lower CD4+ T cells and higher T cell activation and exhaustion markers were noted on CD4+ T and on CD8+ T cells and memory subsets from HIV/DET group, who also produced lower in vitro IFN-gamma, IL-10, IL-13, IL-17A, IL-5 and IL-6 than HIV/UND group. HIV/UND were comparable with CONTROL group in respect to CD4+ T cell counts and T cell activation and exhaustion markers, but with higher in vitro production of ITAC (a chemokine with leukocyte recruitment function), IL-4 and IL-23. An inverse correlation between cytokine production and programmed cell death protein-1 expression on CD4+ T and CD8+ T subsets was detected. Conclusions: Persistent viremia despite ART leads to T cell activation and immune exhaustion with low cytokine production, whereas viral suppression by ART leads to parameters similar to CONTROL, although a different cytokine profile is observed, indicating residual HIV impact despite absence of detectable viremia.

Humoral immune response to vaccine antigens is known to be reduced in perinatally HIV-infected children. Lymphocyte immunophenotyping, humoral immunity to hepatitis B after primary immunization and response to revaccination were evaluated in 40 HIV-infected adolescents on HAART and 23 healthy age-matched controls. Anti-HBs antibody levels >or=10 mIU/mL were found in 18/40 (40.5%) of the HIV-infected adolescents and 18/23 (78.3%) of the HIV-negative adolescents from Control group. Adolescents of HIV group with anti-HBs>or=1 0 mIU/mL presented a higher CD4+ T cell percentage, higher naïve and central memory CD8+ T cell percentages and lower immune activation markers. After revaccination, 12/18 (66.7%) adolescents of HIV group responded. Those adolescents who did not respond to revaccination presented a lower CD4+ T cell percentage, higher immune activation markers and more frequently detectable HIV viral load. We concluded that lower immune activation, higher CD4+ T cell percentage and better control of HIV replication may be associated with hepatitis B vaccine response.

Objective: To evaluate the prevalence of hepatitis A virus antibodies in HIV-exposed and/or HIV-infected children and adolescents.Methods: Between September 1996 and August 2002, 352 patients (200 exposed, but not HIV-infected and 152 HIV exposed and infected) were included in this study. These children and adolescents (age ranged between 1 and 14 years) were all followed up at the Pediatric AIDS Clinic of the Federal University of São Paulo (UNIFESP) and had anti-HAV antibodies determined by a commercially available ELISA method (tests for total anti-HAV antibodies and specific IgM antibodies) (Dia Sorin and Radim). Statistical analyses were done with chi-squared and t test.Results: The prevalence of hepatitis A virus antibodies in HIVinfected and HIV-exposed, but uninfected patients was 34% and 19.7%, respectively. We noticed that in the age range between 2 years and 10 years, the group of HIV-infected children presented a higher prevalence of hepatitis A virus antibodies (35.5%) than the group of uninfected children (16.7%) (p = 0.005). In the HIV infected group, children from B and C categories had a prevalence of hepatitis A virus antibodies (40.5%) higher than N and A categories (24.1%) (p = 0.042). Mean age did not differ when children from B and C categories were compared with N and A categories (5.18 and 5.66 years, respectively) (p = 0.617). Conclusions:The prevalence of hepatitis A virus antibodies in HIV exposed and/or infected children and adolescents between 1 and 14 years old was 26%. Considering the possibility of HIV infection aggravation when associated with hepatitis A virus infection, we suggest that hepatitis A virus inactivated vaccine should be administered to these patients. ResumoObjetivo: Avaliar a prevalência de anticorpos contra o vírus da hepatite A em crianças e adolescentes expostos e/ou infectados pelo HIV.Métodos: Entre setembro de 1996 e agosto de 2002, foram incluídos neste estudo 352 crianças e adolescentes, filhos de mães soropositivas para o HIV (200 expostos e não-infectados pelo HIV, e 152 expostos e infectados pelo HIV). Essas crianças e adolescentes, com idade entre 1 e 14 anos, acompanhados no Ambulatório de AIDS Pediátrica da Universidade Federal de São Paulo (UNIFESP), fizeram teste sorológico contra hepatite A como parte da avaliação de rotina. A dosagem de anticorpos anti-HAV (anticorpos totais e IgM) foi realizada através do método ELISA (Dia Sorin e Radim). A comparação das faixas etárias entre os grupos foi feita utilizando o teste do qui-quadrado e, para comparar as médias de idade das categorias clínicas entre as crianças infectadas, utilizou-se o teste t.Resultados: A prevalência de anticorpos contra o vírus da hepatite A foi de 34% nos pacientes infectados e expostos ao HIV e 19,7% no grupo de soro-revertidos (expostos ao HIV e não-infectados). Estratificando a amostra por faixa etária, observamos que, para as crianças de 2 a 10 anos, o grupo de infectados pelo HIV apresentou prevalência de anticorpos para o vírus hepatite A (35,5%) maior do que o gr...

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