Regina Célia de Menezes Succi

Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal.

Background In utero transmission of HIV-1 occurs on average in only 3%–15% of HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus, despite potential exposure, the majority of infants remain uninfected. Weak HIV-1-specific T-cell responses have been detected in children exposed to HIV-1, and potentially contribute to protection against infection. We, and others, have recently shown that the removal of CD4+CD25+ T-regulatory (Treg) cells can reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults. Here, we hypothesized that Treg cells could suppress HIV-1-specific immune responses in young children. Methodology/Principal Findings We studied two cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation, and cell-mediated immune responses. We detected high levels of CD4+CD25+CD127− Treg cells and low levels of CD4+ and CD8+ T cell activation in the cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses in all of the children exposed to the virus. These T-cell responses were not seen in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of CD4+CD25+ Treg cells from the cord blood of EU newborns strikingly augmented both CD4+ and CD8+ HIV-1-specific immune responses. Conclusions/Significance This study provides new evidence that EU infants can mount strong HIV-1-specific T cell responses, and that in utero CD4+CD25+ T-regulatory cells may be contributing to the lack of vertical transmission by reducing T cell activation.

Alterações metabólicas da síndrome lipodistrófica do HIV

A introducao da highly active antiretroviral therapy (HAART) - terapia anti-retroviral fortemente ativa - vem reduzindo a morbidade e a mortalidade em pacientes infectados com o virus da imunodeficiencia humana (HIV). Entretanto, tratamentos prolongados, com combinacoes de drogas, sao de dificil manutencao devido a ma aderencia e aos efeitos toxicos. O tratamento com agentes anti-retrovirais, especialmente os inibidores da protease, fez surgir uma sindrome caracterizada por redistribuicao anormal da gordura corporal, alteracoes no metabolismo glicemico, resistencia insulinica e dislipidemia, chamada de sindrome lipodistrofica do HIV (SLHIV). Atualmente nao existe nenhum consenso para prevencao ou tratamento da sindrome, cuja causa permanece desconhecida. Esta revisao enfatiza os achados clinicos e dados da literatura a respeito da SLHIV, pois um melhor entendimento desta sindrome por infectologistas, cardiologistas e endocrinologistas e essencial para o manejo da doenca.The introduction of highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with the human immunodeficiency virus (HIV). However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. Treatment with antiretroviral agents--protease inhibitors in particular--has uncovered a syndrome of abnormal fat redistribution, impaired glucose metabolism, insulin resistance and dyslipidemia, collectively termed lipodystrophy syndrome (SLHIV). Nowadays, no clinical guidelines are available for the prevention or treatment of SLHIV, and its cause have yet to be totally elucidated. This review emphasizes the clinical features and the data from previous studies about the SLHIV taking into account that a better understanding of this syndrome for HIV specialists, cardiologists and endocrinologists is fundamental for the disease control.The introduction of highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with the human immunodeficiency virus (HIV). However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. Treatment with antiretroviral agents - protease inhibitors in particular - has uncovered a syndrome of abnormal fat redistribution, impaired glucose metabolism, insulin resistance and dyslipidemia, collectively termed lipodystrophy syndrome (SLHIV). Nowadays, no clinical guidelines are available for the prevention or treatment of SLHIV, and its cause have yet to be totally elucidated. This review emphasizes the clinical features and the data from previous studies about the SLHIV taking into account that a better understanding of this syndrome for HIV specialists, cardiologists and endocrinologists is fundamental for the disease control.

Mother-to-child transmission of HIV in Brazil during the years 2000 and 2001: results of a multi-centric study

The objective of this study was to assess mother-to-child transmission rates of HIV in Brazil during the years 2000 and 2001, and to identify the maternal and neonatal variables that were associated with this transmission. It was a cross-sectional, observational study with retrospective data obtained from patient medical records. The children were followed at 63 medical sites situated in five geographical macro-regions of the country (20 States and the Federal Capital). Children enrolled were those that were born of HIV-infected mothers and it was necessary for the mothers to present documented proof of HIV-infection before or during pregnancy, at time of delivery or in the first three months after delivery. There were 2,924 children enrolled and mother-to-child transmission rates of HIV were 8.6% (95%CI: 7.2-10.2) for the year 2000 and 7.1% (95%CI: 5.8-8.6) for the year 2001. The following variables were associated with lower mother-to-child transmission rates of HIV: elective cesarean section, diagnosis of mothers infection before or during pregnancy, access to HIV viral load and T CD4+ lymphocyte count during prenatal care, greater birth weight and avoidance of breastfeeding.

Prevention of mother-to-child transmission of HIV in São Paulo State, Brazil: an update.

Background:São Paulo State has had the largest number of paediatric AIDS cases in Brazil. Since 1996, São Paulo (and Brazil nationally) has implemented an aggressive programme to reduce perinatal transmission. We have gathered available indicators to examine the programmes impact. Methods:We obtained data on reported AIDS cases from the AIDS surveillance system; data on the number of mother/infant pairs treated with zidovudine from the state logistics office responsible for distributing HIV medication; and the rates of perinatal transmission from a multicity study of the Brazilian Pediatric Society that includes a number of São Paulo facilities, which were compared with an independent study in 1995. The years for which data were available varied according to the source of the indicator. Results:Annual reported cases of AIDS as a result of perinatal transmission fell 58.9% from 1997 to 2002. The number of cases treated with zidovudine increased 73.7% from 1997 to 2004. The rate of perinatal transmission among babies born to HIV-positive mothers fell from 16% in 1995 to 2.4% in 2002 in the reference clinics that participated in the Brazilian Pediatric Society study. Conclusion:Both process and outcome indicators point to the effectiveness of efforts to reduce perinatal transmission in São Paulo State.

Improving survival among Brazilian children with perinatally-acquired AIDS

UNLABELLED Brazil was the first developing country to provide free, universal access to antiretroviral treatment for AIDS patients. The Brazilian experience thus provides the first evidence regarding the impact of such treatment on the survival of perinatally acquired AIDS cases in the developing world. MATERIAL AND METHODS This retrospective cohort study used medical record reviews to examine characteristics and trends in the survival of a representative sample of 914 perinatally acquired AIDS cases in 10 Brazilian cities diagnosed between 1983 and 1998. RESULTS Survival time increased steadily and substantially. Whereas half of the children died within 20 months of diagnosis at the beginning of the epidemic, 75% of children diagnosed in 1997 and 1998 were still alive after four years of follow-up. CONCLUSIONS Advances in management and treatment have made a great difference in the survival of Brazilian children with AIDS. These results argue strongly for making such treatment available to children in the entire developing world.

Low CD4+ T-Cell Levels and B-Cell Apoptosis in Vertically HIV-exposed Noninfected Children and Adolescents

Lymphocyte subsets, activation markers and apoptosis were assessed in 20 HIV-exposed noninfected (ENI) children born to HIV-infected women who were or not exposed to antiretroviral (ARV) drugs during pregnancy and early infancy. ENI children and adolescents were aged 6-18 years and they were compared to 25 age-matched healthy non-HIV-exposed children and adolescents (Control). ENI individuals presented lower CD4(+) T cells/mm(3) than Control group (control: 1120.3 vs. ENI: 876.3; t-test, p = 0.030). ENI individuals had higher B-cell apoptosis than Control group (Control: 36.6%, ARV exposed: 82.3%, ARV nonexposed: 68.5%; Kruskal-Wallis, p < 0.05), but no statistical difference was noticed between those exposed and not exposed to ARV. Immune activation in CD4(+) T, CD8(+) T and in B cells was comparable in ENI and in Control children and adolescents. Subtle long-term immune alterations might persist among ENI individuals, but the clinical consequences if any are unknown, and these children require continued monitoring.

Immunogenicity and Tolerability of Hepatitis A Vaccine in HIV-Infected Children

The immunogenicity and tolerability of hepatitis A virus vaccine was evaluated in a group of 32 children with human immunodeficiency virus (HIV) infection and 27 children with seroreversion. After 2 doses of vaccine, 100% of children experienced seroconversion with good toleration of the vaccine. There were no differences in variation of virus load between immunized HIV-positive children and a group of 31 nonimmunized HIV-positive children with similar characteristics.

AIDS by mother-to-child transmission: Survival analysis of cases followed from 1983 to 2002 in different regions of Brazil.

Antiretroviral therapy contributes to decreasing morbidity and mortality, and ultimately to increasing survival. In Brazil, there are regional differences in HIV epidemiology regarding pregnant women and children with HIV/AIDS. This study evaluates survival time after AIDS diagnosis in 914 children infected by mother-to-child transmission, reported between 1983 and 1998 and followed until 2002, in Brazils five regions. Time between birth and HIV diagnosis decreased over the years, mainly in the South and Southeast Regions. There was a significant improvement in survival; more than 75% of cases were still living four years after diagnosis in the 1997-1998 group. This Brazilian study demonstrates that even with regional inequalities in health care infrastructure it is possible for a developing country to establish an effective system of universal and free access to antiretroviral therapy that produces a significant increase in survival for children with AIDS.

Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART)

The aim of this study was to evaluate the genotypic resistance profiles of HIV-1 in children failing highly active antiretroviral therapy (HAART). Forty-one children (median age = 67 months) receiving HAART were submitted to genotypic testing when virological failure was detected. cDNA was extracted from PBMCs and amplified by nested PCR for the reverse transcriptase and protease regions of the pol gene. Drug resistance genotypes were determined from DNA sequencing. According to the genotypic analysis, 12/36 (33.3%) and 6/36 (16.6%) children showed resistance and possible resistance, respectively, to ZDV; 5/36 (14%) and 4/36 (11.1%), respectively, showed resistance and possible resistance to ddI; 4/36 (11.1%) showed resistance to 3TC and D4T; and 3/36 (8.3%) showed resistance to Abacavir. A high percentage (54%) of children exhibited mutations conferring resistance to NNRTI class drugs. Respective rates of resistance and possible resistance to PIs were: RTV (12.2%, 7.3%); APV (2.4%, 12.1%); SQV(0%, 12.1%); IDV (14.6%, 4.9%), NFV (22%, 4.9%), LPV/RTV (2.4%, 12.1%). Overall, 37/41 (90%) children exhibited virus with mutations related to drug resistance, while 9% exhibited resistance to all three antiretroviral drug classes.

Rubella immunization in human immunodeficiency virus type 1-infected children: cause for concern in vaccination strategies.

Background: HIV infection can have important although sometimes unexpected consequences, such as contributing to enlargement of the pool of rubella-susceptible children. Methods: At the Federal University of São Paulo, Brazil, we assessed response to rubella immunization at 15 months of age in 15 human immunodeficiency virus type 1 (HIV)-infected children, 20 seroreverted children (SR) and 18 healthy control children born to HIV-seronegative mothers (CON). Blood samples were collected before and 3 months after vaccination. All HIV-infected children had started highly active antiretroviral therapy during their first 6 months of life. Serum samples were tested with a rubella IgG enzyme-linked immunosorbent assay kit. Results: HIV children in immunologic categories 2/3 had lower rubella antibody titers (geometric mean, 33 IU/mL) than those from CON (125 IU/mL) and SR group (236 IU/mL) (Tukey, P = 0.01). Antibody values after vaccination were positively associated with CD4 T cell numbers and negatively associated with HIV viral load assessed immediately before vaccination. The percentage of children with protective antibodies after vaccination (above 10.0 IU/mL) was also significantly different among groups (Fishers exact test, P = 0.013): CON, 94%; SR, 100%; HIV category 1, 100%; HIV category 2/3, 62%. Conclusions: HIV-infected children with a preserved immune system at measles-mumps-rubella immunization can have a good response to rubella vaccine. In contrast, those in more advanced categories for HIV infection respond poorly.