Survival After Hematopoietic Stem Cell Transplantation in Severe Combined Immunodeficiency (SCID): A Worldwide Review of the Prognostic Variables.

This study aims to perform an extensive review of the literature that evaluates various factors that affect the survival rates of patients with severe combined immunodeficiency (SCID) after hematopoietic stem cell transplantation (HSCT) in developed and developing countries. An extensive search of the literature was made in four different databases (PubMed, Embase, Scopus, and Web of Science). The search was carried out in December 2022 and updated in July 2023, and the terms such as "hematopoietic stem cell transplantation," "bone marrow transplant," "mortality," "opportunistic infections," and "survival" associated with "severe combined immunodeficiency" were sought based on the MeSH terms. The language of the articles was "English," and only articles published from 2000 onwards were selected. Twenty-three articles fulfilled the inclusion criteria for review and data extraction. The data collected corroborates that early HSCT, but above all, HSCT in patients without active infections, is related to better overall survival. The universal implementation of newborn screening for SCID will be a fundamental pillar for enabling most transplants to be carried out in this "ideal scenario" at an early age and free from infection. HSCT with an HLA-identical sibling donor is also associated with better survival rates, but this is the least common scenario. For this reason, transplantation with matched unrelated donors (MUD) and mismatched related donors (mMRD/Haploidentical) appear as alternatives. The results obtained with MUD are improving and show survival rates similar to those of MSD, as well as they do not require manipulation of the graft with expensive technologies. However, they still have high rates of complications after HSCT. Transplants with mMRD/Haplo are performed just in a few large centers because of the high costs of the technology to perform CD3/CD19 depletion and TCRαß/CD19 depletion or CD34 + selection techniques in vitro. The new possibility of in vivo T cell depletion using post-transplant cyclophosphamide could also be a viable alternative for performing mMRD transplants in centers that do not have this technology, especially in developing countries.

Investigation of Mortality of Hereditary Angioedema in a Reference Center in Brazil.

BACKGROUND: Hereditary angioedema (HAE) is known for mortality when it is not treated properly. Many advances have occurred over the past decades that affected patients' lives. However, not all patient populations have access to the same diagnosis and treatment resources. OBJECTIVE: To evaluate mortality from HAE in a large cohort in a reference center in Brazil. Furthermore, the research intended to describe patients' life span, the asphyxia evolution, and factors related to the fatal outcome. METHODS: A cohort of 433 patients from 46 families was evaluated in this prospective and retrospective study. Families were organized in clusters and were given a verbal autopsy to arrange data collection for the deaths and analyze symptoms during life. Causes of death were classified as deaths from laryngeal edema (LE) or other causes. RESULTS: Of 433 patients evaluated, 254 were not given the diagnosis of HAE. A total of 75 fatal events were evaluated. Only 10 of 75 patients were given the diagnosis of HAE before death, and the HAE diagnosis was made after death in 65 of 75 patients using verbal autopsy. The final cause of death after the investigation was asphyxiation owing to LE in 39 of 75 (52%) and deaths owing to other causes in 36 of 75 (48%). Ten deaths had occurred in the past decade. Time from onset of symptoms to seeking medical assistance was a median of 4 hours, and the time to death was a median of 8 hours. Three patients received fresh-frozen plasma and none received medications specific to HAE attacks. Throat pain or discomfort was the most common symptom, experienced by 71.8% of patients. The most common mistaken diagnosis at the original death certificate was allergy or anaphylaxis. The life span of patients who died of LE was reduced by 20 years compared with those who died of other causes. CONCLUSIONS: Hereditary angioedema remains a threat to life in the studied population. The large number of patients who do not receive a diagnosis makes the situation even more severe and is responsible for most deaths. Death analyses add knowledge to an understanding of the diseases and their impact on patients' lives, improving the targeting of public health efforts.

The Mortality from Hereditary Angioedema Worldwide: a Review of the Real-World Data Literature.

This study aims to review the global mortality secondary to laryngeal edema in patients diagnosed with hereditary angioedema and their relatives over the years, as well as to describe epidemiological and clinical findings associated with this outcome. An extensive search of the literature was made in PubMed, Scopus, and Embase to identify mortality rates secondary to laryngeal edema in patients with hereditary angioedema. The search was carried out in September of 2020 and in April of 2021, and keywords based on the MeSH terms were searched in three databases. The filter of language was used for finding only articles in English, and there was no limit to the year of publication. A total of twenty-three articles fulfilled the inclusion criteria for review and data extraction. The analyzed studies included 3292 patients and 411 deaths from asphyxia due to laryngeal edema. One hundred and three deaths in close relatives were described as secondary to the same cause. The main findings were summarized in tables: year and place of publication, the number of patients and deaths from laryngeal edema, patients previously diagnosed, and death age. Death rates from laryngeal edema had an average of one death for every 20 patients. Eight studies reported deaths in relatives. For every 7.4 patients in these studies, one relative died. The percentage among deaths in general associated with laryngeal edema was evaluated in three studies (32.7%, 44.4%, and 56%). The high frequency of this outcome suggests that deaths still occur, and improvement of hereditary angioedema treatment still needs to be met.

The Challenges in the Follow-Up and Treatment of Brazilian Children with Hereditary Angioedema.

INTRODUCTION: Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare autosomal dominant disease. Although the first symptoms can appear in childhood, the diagnosis's delay has a strong impact on the patient's quality of life. We analyzed clinical and laboratory characteristics and the drug therapy of pediatric patients with HAE in Brazil. METHODS: Medical records from 18 reference centers of HAE patients under 18 years of age were evaluated after confirmed diagnosis was performed by quantitative and/or functional C1-INH. RESULTS: A total of 95 participants (51 M:44 F; mean age: 7 years old) out of 17 centers were included; 15 asymptomatic cases were identified through family history and genetic screening. Angioedema attacks affected the extremities (73.5%), gastrointestinal tract (57%), face (50%), lips (42.5%), eyelids (23.7%), genitals (23.7%), upper airways (10%), and tongue (6.3%). Family history was present in 84% of patients, and the mean delay in the diagnosis was 3.9 years. Long-term prophylaxis (51/80) was performed with tranexamic acid (39/80) and androgens (13/80); and short-term prophylaxis (9/80) was performed with tranexamic acid (6/80) and danazol (3/80). On-demand therapy (35/80) was prescribed: icatibant in 7/35, fresh frozen plasma in 16/35, C1-INH plasma-derived in 11/35, and tranexamic acid in 12/35 patients. CONCLUSIONS: This is the first study on HAE pediatric patients in Latin America. Clinical manifestations were similar to adults. Drugs such as androgens and tranexamic acid were indicated off-label, probably due to restricted access to specific drugs. Educational programs should address pediatricians to reduce late diagnosis and tailored child therapy.

Vertical Transmission of HIV-1 in the Metropolitan Area of Belo Horizonte, Brazil: 2006-2014.

OBJECTIVE: To revise HIV-1 vertical transmission (VT) rates in the metropolitan area of Belo Horizonte, Brazil, from January of 2006 to December of 2014. METHODS: Descriptive study of a prospective cohort of HIV-1-infected pregnant women and their children, monitored by the Maternal and Child HIV/Aids Research Group of Research Group at Faculty of Medicine of Universidade Federal de Minas Gerais, Brazil. RESULTS: The VT general rate was 1.9% (13/673; confidence interval [CI] 95%: 1.0-3.3). The extensive use of combined highly active antiretroviral therapy (HAART) (89.7%; 583/650) strongly impacted the reduction of VT during this period. Maternal viral load (VL) higher than 1,000 copies/mL showed significant association with VT (OR:6.6; CI 95%:1.3-33.3). Maternal breastfeeding was described in 10 cases in this cohort (1.5%; CI 95%: 0.7-2.7), but it was not associated with VT. CONCLUSION: The present cohort data were coherent with the low VT rate described in other global populations, and it was considerably lower in comparison to the results of the same cohort during the period of 1998-2005, when the VT rate was 6.2%. These data confirm the efficiency of the National Guidelines, and emphasize the importance of adopting the international recommended procedures for prevention of mother-to-child transmission (MTCT) of HIV.

OBJETIVO: Rever as taxas de transmissão vertical (TV) do HIV-1 na área metropolitana de Belo Horizonte, Brasil, de janeiro de 2006 a dezembro de 2014. MéTODOS: Estudo descritivo de uma coorte prospectiva de gestantes infectadas pelo HIV-1 e seus filhos, monitorados pelo Grupo de Pesquisa em HIV/Aids Materno-Infantil, da Faculdade de Medicina da Universidade Federal de Minas Gerais, Brasil. RESULTADOS: A taxa geral de TV foi de 1,9% (13/673; intervalo de confiança [IC] 95%: 1,0­3,3). O uso extensivo de terapia antirretroviral combinada (TARVc) (89,7%; 583/650) impactou fortemente a redução de TV durante este período. Carga viral materna superior a 1.000 cópias/mL mostrou associação significante com TV (OR: 6,6; IC 95%:1,3­33,3). A amamentação materna foi descrita em 10 casos nesta coorte (1,5%; IC 95%: 0,7­2,7), mas não foi associada à TV. CONCLUSãO: Os dados atuais da coorte foram coerentes com a baixa taxa de TV descrita em outras populações globais, e foi consideravelmente menor em comparação com os resultados da mesma coorte no período de 1998­2005, quando a taxa de TV foi de 6,2%. Esses dados confirmam a eficiência das Diretrizes Nacionais, e enfatizam a importância de adotar os procedimentos internacionais recomendados para a prevenção da transmissão do HIV da mãe para o filho.

[Prevalence of congenital and perinatal infection in HIV positive pregnant in Belo Horizonte metropolitan region]. / Prevalência de infecções congênitas e perinatais em gestantes HIV positivas da região metropolitana de Belo Horizonte.

PURPOSE: To evaluate the prevalence of toxoplasmosis, rubella, cytomegalovirus, hepatitis B&C and syphilis (Torchs) in a cohort pregnant women and to identify the sociodemographic, clinical and laboratory factors. METHODS: A total of 1,573 HIV-infected pregnant women from a Brazilian metropolitan region were studied between 1998 and 2013. The results of serological tests were available for 704 (44.8%) pregnant women. Pregnant women were considered to be Torchs positive (Gtp) when they had positive results for at least one of these infections, and to be Torchs negative (Gtn) when they had negative results for all of them. Maternal covariables were: age, marital status, educational level, time and mode of infection, CD4 lymphocyte count, viral load at delivery, and use of antiretroviral therapy (ARV). Neonatal covariables were: HIV infection, prematurity, low birth weight, neonatal complications, abortion and neonatal death. Odds ratios with 95% confidence interval were used to quantify the association between maternal and neonatal variables and the presence of Torchs. RESULTS: Among 704 pregnant women, 70 (9.9%; 95%CI 7.8-12.4) had positive serological tests for any Torchs factor. The individual prevalence rates were: 1.5% (10/685) for toxoplasmosis; 1.3% (8/618) for rubella; 1.3% (8/597) for cytomegalovirus; 0.9% (6/653) for hepatitis B and 3.7% (20/545) for hepatitis C; and 3.8% (25/664) for syphilis. The HIV Vertical HIV transmission was 4.6% among Gtp pregnant women and 1.2% among Gtn women. Antiretroviral therapy (ARV), vertical transmission, low birth weight and neonatal complications were significantly associated with Torchs positivity in univariate analysis. CONCLUSIONS: The Torchs prevalence found in the study was high for some infections. These findings emphasize the need to promote serological Torchs screening for all pregnant women, especially HIV-infected women, so that an early diagnosis can be made and treatment interventions can be implemented to prevent vertical HIV transmission.

Prevalência de infecções congênitas e perinatais em gestantes HIV positivas da região metropolitana de Belo Horizonte / Prevalence of congenital and perinatal infection in HIV positive pregnant in Belo Horizonte metropolitan region

OBJETIVOS: Avaliar a prevalência de toxoplasmose, rubéola, citomegalovirose, hepatites B e C e sífilis (Torchs) em uma coorte de gestantes, bem como identificar os fatores sociodemográficos, clínicos e laboratoriais.MÉTODOS: Entre 1998 e 2013, foram atendidas 1.573 gestantes com sorologia positiva para o HIV em área metropolitana do Brasil, das quais 704 (44,8%) foram submetidas a algum dos testes sorológicos. Gestantes Torchs positivas (Gtp) foram consideradas aquelas com resultado positivo para uma dessas infecções, e gestantes Torchs negativas (Gtn) aquelas com resultados negativos para todas elas. As variáveis maternas investigadas foram: idade, estado civil, escolaridade, momento e forma de contágio da infeccção pelo HIV, contagem de linfócitos TCD4+, carga viral plasmática do HIV próxima ao parto e uso de terapia antirretroviral durante a gestação. As variáveis neonatais investigadas foram ocorrência de: transmissão vertical, prematuridade, baixo peso ao nascimento, complicações fetais, aborto e óbito fetal. Foram utilizadas razões de chance com intervalo de confiança de 95% para quantificar a associação entre as variáveis maternas e neonatais e a presença de Torchs.RESULTADOS: Entre as 704 gestantes, 70 (9,9%; IC95% 7,8-12,4) tinham alguma sorologia positiva para Torchs. Foram encontradas taxas: 1,5% (10/685) para a toxoplasmose; 1,3% (8/618) para rubéola; 1,3% (8/597) para citomegalovirose; 0,9% (6/653) para hepatite B e 3,7% (20/545) para hepatite C; e 3,8% (25/664) para sífilis. A transmissão vertical do HIV entre as gestantes Gtp foi 4,6% e de 1,2% entre as Gtn. As variáveis associadas à presença de Torchs na análise univariada foram: uso de terapia antirretroviral, transmissão vertical do HIV, baixo peso ao nascimento e complicações fetais.CONCLUSÃO: A prevalência das Torchs mostrou-se elevada para algumas infecções. Conclui-se que é importante manter o rastreamento de Torchs na gravidez, especialmente nas gestantes HIV positivas, para que se possa estabelecer diagnóstico e tratamento, e/ou medidas preventivas para evitar a transmissão materno-fetal.

PURPOSE: To evaluate the prevalence of toxoplasmosis, rubella, cytomegalovirus, hepatitis B&C and syphilis (Torchs) in a cohort pregnant women and to identify the sociodemographic, clinical and laboratory factors.METHODS: A total of 1,573 HIV-infected pregnant women from a Brazilian metropolitan region were studied between 1998 and 2013. The results of serological tests were available for 704 (44.8%) pregnant women. Pregnant women were considered to be Torchs positive (Gtp) when they had positive results for at least one of these infections, and to be Torchs negative (Gtn) when they had negative results for all of them. Maternal covariables were: age, marital status, educational level, time and mode of infection, CD4 lymphocyte count, viral load at delivery, and use of antiretroviral therapy (ARV). Neonatal covariables were: HIV infection, prematurity, low birth weight, neonatal complications, abortion and neonatal death. Odds ratios with 95% confidence interval were used to quantify the association between maternal and neonatal variables and the presence of Torchs.RESULTS: Among 704 pregnant women, 70 (9.9%; 95%CI 7.8-12.4) had positive serological tests for any Torchs factor. The individual prevalence rates were: 1.5% (10/685) for toxoplasmosis; 1.3% (8/618) for rubella; 1.3% (8/597) for cytomegalovirus; 0.9% (6/653) for hepatitis B and 3.7% (20/545) for hepatitis C; and 3.8% (25/664) for syphilis. The HIV Vertical HIV transmission was 4.6% among Gtp pregnant women and 1.2% among Gtn women. Antiretroviral therapy (ARV), vertical transmission, low birth weight and neonatal complications were significantly associated with Torchs positivity in univariate analysis.CONCLUSIONS: The Torchs prevalence found in the study was high for some infections. These findings emphasize the need to promote serological Torchs screening for all pregnant women, especially HIV-infected women, so that an early diagnosis can be made and treatment interventions can be implemented to prevent vertical HIV transmission.

Long-term efficacy and safety of tenofovir disoproxil fumarate in HIV-1-infected adolescents failing antiretroviral therapy: the final results of study GS-US-104-0321.

BACKGROUND: Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321). METHODS: HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. RESULTS: Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. CONCLUSIONS: Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.

[Illicit drug use by pregnant women infected with HIV]. / Uso de drogas ilícitas por gestantes infectadas pelo HIV.

PURPOSE: To determine if illicit drug use increases the vertical transmission of HIV, to identify the risk factors involved in mother and child health and the prevalence of illicit drug use among these pregnant women. METHODS: Sixty-four (7.6%) of 845 pregnant women from the metropolitan region of Belo Horizonte, Minas Gerais, Brazil, attended in the service between October 1997 and February 2012 reported the use of illicit drugs. Cases were HIV-positive drug users (n=64) and controls were women who did not use drugs (n=192). Three controls were selected for each case. Several conditions of exposure were considered in the control group such as tobacco use, alcohol use, alcohol and tobacco use, maternal age, educational level, ethnicity, and marital status. Problems during the prenatal period, delivery and postpartum, vertical HIV transmission and neonatal outcomes were also investigated. RESULTS: Univariate analysis showed as significant variables: maternal age, tobacco use, number of prenatal care visits, antiretroviral therapy, mode of infection, and viral load at delivery. Logistic regression revealed as significant variables: maternal age (less than 25 years); tobacco use, and number of prenatal care visits (less than 6). The vertical transmission of HIV was 4,8% (95%CI 1.7-13.3) among drug users and 2,1% (95%CI 0.8-5.2) in the control group, with no statistically significant difference between groups. Neonatal complications were more frequent among drug users, but also with no statistically significant difference between groups. CONCLUSION: The use of illicit drug is frequent during pregnancy among HIV-infected women. The approach to illicit drug use should be routine during prenatal care visits. These women are more discriminated against and tend to deny their habits or do not seek prenatal care. There was no difference in vertical virus transmission between groups, probably indicating adherence to antiretroviral use for antiretroviral therapies during pregnancy.

Uso de drogas ilícitas por gestantes infectadas pelo HIV / Illicit drug use by pregnant women infected with HIV

OBJETIVO: Determinar se o uso de drogas ilícitas aumenta a transmissão vertical do HIV, identificar os fatores de risco envolvidos na saúde materno-infantil e a prevalência do uso de drogas entre essas gestantes. MÉTODOS: Entre 845 gestantes da região metropolitana de Belo Horizonte, Minas Gerais, atendidas no serviço entre outubro de 1997 e fevereiro de 2012, 64 (7,6%) afirmaram usar drogas ilícitas. Os casos são as gestantes HIV positivas usuárias de drogas ilícitas (n=64) e os controles as não usuárias (n=192). Para cada caso foram selecionados três controles. Consideraram-se as diferentes exposições/condições no grupo controle como: tabagismo; etilismo; uso de tabaco e álcool; idade materna; escolaridade; etnia; e estado civil. Foram investigadas também intercorrências no pré-natal, parto e puerpério, taxa de transmissão vertical e resultados neonatais. RESULTADOS: As variáveis com significância estatística na análise univariada foram: idade materna; uso de tabaco; número de consultas de pré-natal; tipo de terapia antirretroviral; forma de contágio e carga viral na época do parto. A regressão logística mostrou como significantes: idade materna (menores de 25 anos), uso de tabaco e o número de consultas de pré-natal (menos de 6). A transmissão vertical entre usuárias foi de 4,8% (IC95% 1,7–13,3) e, no grupo controle, 2,1% (IC95% 0,8–5,2), sem diferença significante. As complicações neonatais foram mais frequentes entre os recém-nascidos das gestantes usuárias, também sem diferença significante. CONCLUSÃO: O uso de drogas ilícitas na gravidez entre mulheres infectadas pelo HIV é frequente. Assim, a abordagem sobre o uso dessas drogas deve fazer parte da rotina pré-natal. Essas ...

PURPOSE: To determine if illicit drug use increases the vertical transmission of HIV, to identify the risk factors involved in mother and child health and the prevalence of illicit drug use among these pregnant women. METHODS: Sixty-four (7.6%) of 845 pregnant women from the metropolitan region of Belo Horizonte, Minas Gerais, Brazil, attended in the service between October 1997 and February 2012 reported the use of illicit drugs. Cases were HIV-positive drug users (n=64) and controls were women who did not use drugs (n=192). Three controls were selected for each case. Several conditions of exposure were considered in the control group such as tobacco use, alcohol use, alcohol and tobacco use, maternal age, educational level, ethnicity, and marital status. Problems during the prenatal period, delivery and postpartum, vertical HIV transmission and neonatal outcomes were also investigated. RESULTS: Univariate analysis showed as significant variables: maternal age, tobacco use, number of prenatal care visits, antiretroviral therapy, mode of infection, and viral load at delivery. Logistic regression revealed as significant variables: maternal age (less than 25 years); tobacco use, and number of prenatal care visits (less than 6). The vertical transmission of HIV was 4,8% (95%CI 1.7–13.3) among drug users and 2,1% (95%CI 0.8–5.2) in the control group, with no statistically significant difference between groups. Neonatal complications were more frequent among drug users, but also with no statistically significant difference between groups. CONCLUSION: The use of illicit drug is frequent during pregnancy among HIV-infected women. The approach to illicit drug use should be routine during prenatal care visits. These women are more discriminated against and tend to deny their habits or do not seek prenatal care. There was no difference in vertical virus transmission between groups, probably indicating adherence to antiretroviral ...

Vírus da imunodeficiência humana adquirida/HIV no período neonatal / Acquired human immunodeficiency virus/ HIV in the neonatal period

O bloqueio da transmissão vertical foi uma das maiores vitórias contra a infecção pelo HIV. Houve redução das taxas de infecção a níveis inferiores a 2% com a aplicação de estratégias como reconhecimento da infecção materna (testagem sorológica anti-HIV ou teste rápido) durante o pré-natal ou no momento do parto, uso de antirretrovirais, via de parto eletiva de acordo com a carga viral e substituição do aleitamento materno pelo uso de fórmula láctea infantil. No Brasil, recomenda-se a utilização de esquema antirretroviral composto de três drogas antirretrovirais de duas classes diferentes a partir da 14a semana de gestação (após o primeiro trimestre) para todas as gestantes infectadas pelo HIV, independentemente dos parâmetros imunológicos ou virológicos, uso de zidovudina por via venosa no momento do parto e de zidovudina para todas as crianças nascidas de mães infectadas pelo HIV, duranteas primeiras quatro semanas de vida. Em situações especiais tem-se sugerido a adição de outros antirretrovirais, como a lamivudina e a nevirapina. Os benefícios do uso materno de drogas antirretrovirais para a prevenção da trasnmissão do HIV para seus filhos são unânimes. A segurança desses regimes em curto prazo já foi demonstrada, mas tem sido descrita associação do uso materno de drogas antirretrovirais e anomalias congênitas, prematuridade, toxicidade mitocondrial, anemia, neutropenia e aumento de enzimas hepáticas. Efeitos graves raramente ocorrem. Ainda é necessário acompanhamento em longo prazo de todasas crianças expostas aos antirretrovirais para responder muitas dúvidas existentes.

Blocking mother-to-child transmission was one of the greatest victories against HIV infection. A reduction in infection rates down to below 2% was achieved by applying strategies such as the recognition of maternal infection (HIV serological testing or rapid test) during the prenatal periodor at delivery, use of antiretrovirals, elective route of delivery according to the patient?s viral load, and replacement of breastfeeding by formula. In Brazil, the recommended regimen includes the use of an anti-retroviral scheme composed of three anti-retroviral drugs from two different classes, from the 14th week of pregnancy (after the first trimester), in all pregnant women infected with HIV regardless of their virological or immunological parameters, use of intravenous zidovudine at the time of delivery, and of zidovudine in all children born to HIV infected mothers during the first four weeks of life. In special situations, adding other antiretrovirals, such as lamivudine and nevirapine, has been suggested. The benefits of maternal use of anti-retroviral drugs to prevent HIV transmission to children are unanimous. The safety of these short-term schemes has already been demonstrated, however, the association between maternal use of antiretrovirals drugs and congenital anomalies, prematurity, mitochondrial toxicity, anemia, neutropenia, and increased liver enzymes have been described. Serious effects rarely occur. Long-term follow-up of all children exposed to antiretroviral drugs is still necessary to answer many existing questions.

Lymphadenitis caused by infection with an isoniazid- and rifampin-resistant strain of Mycobacterium bovis BCG in an infant with IFN-γ/IL-12 pathway defect.

We report a rare case in a female infant (age, 3.5 months) with primary immunodeficiency (IFN-γ/IL-12 pathway defect) who presented with suppurative lymphadenitis after Mycobacterium bovis BCG vaccination. The strain of M. bovis BCG identified was found to be resistant to isoniazid and rifampin. The patient was treated with a special pharmacological regimen involving isoniazid (in a limited, strategic manner), ethambutol, streptomycin, and IFN-γ, after which there was complete resolution of the lesions.

Lymphadenitis caused by infection with an isoniazid- and rifampin-resistant strain of Mycobacterium bovis BCG in an infant with IFN-γ/IL-12 pathway defect / Linfadenite por Mycobacterium bovis BCG resistente a isoniazida e rifampicina em lactente com defeito no eixo IFN-γ/IL-12

We report a rare case in a female infant (age, 3.5 months) with primary immunodeficiency (IFN-γ/IL-12 pathway defect) who presented with suppurative lymphadenitis after Mycobacterium bovis BCG vaccination. The strain of M. bovis BCG identified was found to be resistant to isoniazid and rifampin. The patient was treated with a special pharmacological regimen involving isoniazid (in a limited, strategic manner), ethambutol, streptomycin, and IFN-γ, after which there was complete resolution of the lesions.

Relatamos um caso raro em uma lactente com três meses e meio de idade, portadora de imunodeficiência primária (defeito no eixo IFN-γ/IL-12), que apresentou linfadenite supurativa após a vacinação por Mycobacterium bovis BCG, cepa essa resistente a isoniazida e rifampicina. Após o tratamento com um esquema medicamentoso especial com isoniazida (de forma estratégica e limitada), etambutol, estreptomicina e IFN-γ, houve a cura completa das lesões.

Executive function and processing speed in Brazilian HIV-infected children and adolescents.

BACKGROUND: Cognitive disorders in infants and children who are vertically infected with human immunodeficiency virus (HIV) have been recognized since the inception of the epidemic. OBJECTIVE: The present study investigated neuropsychological performance in a cohort of vertically infected Brazilian children and adolescents who underwent antiretroviral therapy. The neuropsychological tasks were designed to evaluate executive function and processing speed. METHODS: Children and adolescents were recruited at a major research and treatment reference center for human immunodeficiency virus/acquired immunodeficiency syndrome (HIV) in Minas Gerais, Brazil. Forty-one individuals aged 5 to 17 years were enrolled. Twelve were mildly symptomatic (HIV-infected group, Centers for Disease Control and Prevention [CDC] class A or B), and 29 had advanced clinical disease (AIDS group, CDC class C). RESULTS: The results showed that HIV-infected children and adolescents exhibited lower performance on neuropsychological tasks than sociodemographically comparable, typically developing controls. Motor and cognitive processing speed and executive function appeared to be the most discriminative domains. CONCLUSION: HIV-infected individuals with more-advanced disease stages exhibited lower performance levels and had greater performance heterogeneity on neuropsychological tasks. Thus, the observed neuropsychological impairments, although more pronounced in participants with more advanced stages of the disease, did not correlate with the variable used (CDC stage).

INTRODUÇÃO: Comprometimentos cognitivos em crianças e adolescentes verticalmente afetadas por HIV são reconhecidos desde do início da epidemia. OBJETIVOS: O presente estudo investigou o desempenho neuropsicológico em uma coorte de crianças e adolescentes verticalmente infectadas por HIV e que fazem uso da terapia antirretroviral no Brasil. As tarefas neuropsicológicas foram selecionadas para avaliar, principalmente, funções executivas e velocidade de processamento. MÉTODOS: As crianças e adolescentes foram recrutados em um grande centro de referência de pesquisa e tratamento para o vírus da imunodeficiência humana / síndrome da imunodeficiência adquirida (HIV / AIDS), em Minas Gerais, Brasil. Quarenta e um indivíduos com idade entre 5 e 17 anos foram selecionados. Doze estavam com sintomas leves (grupo infectado pelo HIV, Centros para Controle e Prevenção de Doenças [CDC] Classe A ou B), e 29 tiveram a doença clínica avançada (grupo AIDS, CDC classe C). RESULTADOS: Os resultados mostraram que as crianças e adolescentes infectados pelo HIV apresentaram menor desempenho em tarefas neuropsicológicas quando comparadas com o grupo controle pareado socio-demograficamente. Habilidades motoras, velocidade de processamento e função executiva são os domínios mais discriminativos. CONCLUSÃO: Indivíduos infectados pelo HIV com estágios da doença mais avançados apresentaram níveis mais baixos de desempenho e tiveram maior heterogeneidade no desempenho em tarefas neuropsicológicas. Entretanto, os prejuízos neuropsicológicos observados, apesar de se mostrarem mais pronunciados com estágios mais avançados da doença, não se correlacionaram com a variável utilizada (estágio do CDC).

The gap between knowledge on HIV/AIDS and sexual behavior: a study of teenagers in Vespasiano, Minas Gerais State, Brazil.

The aim of this study was to investigate gaps between knowledge on HIV/AIDS and sexual behavior among teenagers. The study used a cross-sectional design with a representative random sample of 1,158 teenagers (14 to 19 years of age) enrolled in nine public secondary schools and who answered validated questionnaires. Data analysis included descriptive statistics and tests of hypotheses (chi-square, Mann-Whitney and Kruskal-Wallis, Kendall, and Fisher's exact test). The vast majority of the teenagers (98.7%) expressed doubt on at least one question. Condom use during first sexual intercourse was significantly associated with condom use in sexual relations in the previous six months. There was no statistical association between knowledge on HIV/AIDS and frequency of condom use or number of sexual partners. Health actions are needed that link schools to health services, in addition to not only elaborating appropriate information but also valorizing teenagers' individuality in the development of proposals.

The gap between knowledge on HIV/AIDS and sexual behavior: a study of teenagers in Vespasiano, Minas Gerais State, Brazil / A lacuna entre o conhecimento sobre HIV/AIDS e o comportamento sexual: uma investigação com adolescentes de Vespasiano, Minas Gerais, Brasil / La laguna entre el conocimiento sobre VIH/SIDA y el comportamiento sexual: una investigación con adolescentes de Vespasiano, Minas Gerais, Brasil

The aim of this study was to investigate gaps between knowledge on HIV/AIDS and sexual behavior among teenagers. The study used a cross-sectional design with a representative random sample of 1,158 teenagers (14 to 19 years of age) enrolled in nine public secondary schools and who answered validated questionnaires. Data analysis included descriptive statistics and tests of hypotheses (chi-square, Mann-Whitney and Kruskal-Wallis, Kendall, and Fisher's exact test). The vast majority of the teenagers (98.7%) expressed doubt on at least one question. Condom use during first sexual intercourse was significantly associated with condom use in sexual relations in the previous six months. There was no statistical association between knowledge on HIV/AIDS and frequency of condom use or number of sexual partners. Health actions are needed that link schools to health services, in addition to not only elaborating appropriate information but also valorizing teenagers' individuality in the development of proposals.

O objetivo foi investigar as lacunas entre o conhecimento sobre o HIV/AIDS e o comportamento sexual em adolescentes do ensino médio. Delineamento transversal com amostra representativa e aleatória de 1.158 adolescentes entre 14 a 19 anos, matriculados em nove escolas públicas que responderam a questionários validados. A análise dos dados envolveu estatística descritiva e testes de hipóteses (qui-quadrado, Mann-Whitney e Kruskal-Wallis, Kendal e teste exato de Fisher). A maioria dos adolescentes (98,7%) apresentou dúvida em alguma questão proposta. O uso do preservativo na primeira relação sexual influenciou o uso nas relações dos últimos seis meses. Não houve associação estatística entre o conhecimento sobre HIV/AIDS com a frequência do uso de preservativo e a multiplicidade de parceiros sexuais. É necessário a implementação de ações em saúde que articulem a escola aos serviços de saúde e que além de trabalhar a informação, valorizem a individualidade dos adolescentes na construção das propostas.

El objetivo fue investigar las lagunas entre el conocimiento sobre el VIH/SIDA y el comportamiento sexual en adolescentes de enseñanza media. Delineación transversal con muestra representativa y aleatoria de 1.158 adolescentes entre 14 a 19 años, matriculados en nueve escuelas públicas que respondieron a cuestionarios validados. El análisis de los datos implicó estadística descriptiva y tests de hipótesis (chi-cuadrado, Mann-Whitney y Kruskal-Wallis, Kendal y test exacto de Fisher). La mayoría de los adolescentes (98,7%) presentó dudas en alguna cuestión propuesta. El uso del preservativo en la primera relación sexual influenció el uso en las relaciones de los últimos seis meses. No hubo asociación estadística entre el conocimiento sobre VIH/SIDA con la frecuencia del uso de preservativo y la multiplicidad de compañeros sexuales. Es necesaria la implementación de acciones en salud que articulen la escuela a los servicios de salud y que además de trabajar con la información, valoren la individualidad de los adolescentes en la construcción de las propuestas.

Further evidence that the expression of CD38 and HLA-DR(+) in CD8(+) lymphocytes does not correlate to disease progression in HIV-1 vertically infected children.

BACKGROUND: In adults, an increase in CD8(+)CD38(+) T cell levels is a strong indicator of disease progression in HIV infection. However, in children, data are conflicting. Slow-progressing children (SPC) provide an exceptional resource for the investigation and clarification of the immunological and virological mechanisms of natural control of HIV infection and can be used to investigate prognostic indicators of disease progression. OBJECTIVES: To investigate the immune activation status and T regulatory (Treg) cell levels in SPC. STUDY DESIGN: A cross-sectional study was carried out on 28 children 8 years old and older who were vertically infected with HIV. The children were stratified into 3 groups according to their clinical outcome: SPC (anti-retroviral-therapy-naïve; ≥8 years-old; CD4 ≥20%; viral load <25,000 copies), IF/VF (anti-retroviral-therapy but with no therapeutic response), and IS/VS (anti-retroviral therapy with good therapeutic response). Uninfected children (NI) were assessed as healthy control group. RESULTS: A higher percentage of activated CD8(+) T cells were found in all HIV infected children, regardless of the evolution of disease. The activation of CD8(+) T cells was not associated with either viral load or the percentage of CD4(+) T cells. In addition, Treg cell levels did not show any correlation with the clinical outcome or the activation status of CD8(+) T cells. CONCLUSIONS: HIV-1-infected children presented an increased percentage of activated CD8(+) T cells and an unaltered percentage of Treg cells, regardless of their clinical evolution. Thus, these immunological parameters should not be used for prognostic evaluation.

Longitudinal anthropometric assessment of infants born to HIV-1-infected mothers, Belo Horizonte, Southeastern Brazil / Avaliação antropométrica longitudinal de lactentes nascidos de mães infectadas pelo HIV-1 / Evaluación antropométrica longitudinal de lactantes nacidos de madres infectadas por VIH-1

OBJECTIVE: To evaluate the growth parameters in infants who were born to HIV-1-infected mothers. METHODS: The study was a longitudinal evaluation of the z-scores for the weight-for-age (WAZ), weight-for-length (WLZ) and length-for-age (LAZ) data collected from a cohort. A total of 97 non-infected and 33 HIV-infected infants born to HIV-1-infected mothers in Belo Horizonte, Southeastern Brazil, between 1995 and 2003 was studied. The average follow-up period for the infected and non-infected children was 15.8 months (variation: 6.8 to 18.0 months) and 14.3 months (variation: 6.3 to 18.6 months), respectively. A mixed-effects linear regression model was used and was fitted using a restricted maximum likelihood. RESULTS: There was an observed decrease over time in the WAZ, LAZ and WLZ among the infected infants. At six months of age, the mean differences in the WAZ, LAZ and WLZ between the HIV-infected and non-infected infants were 1.02, 0.59, and 0.63 standard deviations, respectively. At 12 months, the mean differences in the WAZ, LAZ and WLZ between the HIV-infected and non-infected infants were 1.15, 1.01, and 0.87 standard deviations, respectively. CONCLUSIONS: The precocious and increasing deterioration of the HIV-infected infants' anthropometric indicators demonstrates the importance of the early identification of HIV-infected infants who are at nutritional risk and the importance of the continuous assessment of nutritional interventions for these infants.

OBJETIVO: Avaliar os parâmetros de crescimento em lactentes nascidos de mães infectadas com o HIV-1. MÉTODOS: Avaliação longitudinal dos z-escores peso-idade (PI), estatura-idade (EI), peso-estatura (PE) foi realizada em uma coorte. Foram estudados 97 lactentes não-infectados e 33 lactentes infectados nascidos de mães infectadas com o HIV-1 em Belo Horizonte, MG, de 1995 a 2003. O tempo mediano de seguimento para os lactentes infectados e não-infectados foi de 15,8 meses (variação: 6,8 a 18,0 meses) e 14,3 meses (variação: 6,3 a 18,6 meses), respectivamente. Utilizou-se o modelo de regressão linear de efeitos mistos ajustado por máxima verossimilhança restrita para construir as curvas de crescimento. RESULTADOS: Os z-escores PI, EI e PE dos lactentes infectados com o HIV-1 apresentaram decréscimo. Aos seis meses, a diferença média nos z-escores PI, EI e PE entre lactentes infectados e não-infectados com o HIV era, respectivamente, 1,02, 0,59 e 0,63 desvios-padrão. Aos 12 meses, a diferença média nos z-escores PI, EI e PE entre lactentes infectados e não-infectados era, respectivamente, 1,15, 1,01 e 0,87 desvios-padrão. CONCLUSÕES: O comprometimento precoce e crescente dos indicadores antropométricos de crianças infectadas com o HIV-1 mostra a importância de identificar precocemente crianças infectadas com o HIV que estão em risco nutricional e a necessidade de se avaliarem continuamente as intervenções nutricionais adotadas.

OBJETIVO: Evaluar los parámetros de crecimiento en lactantes nacidos de madres infectadas con el VIH-1. MÉTODOS: Evaluación longitudinal de los z-escores peso-edad (PI), estatura-edad (EI), peso-estatura (PE) fue realizada en una cohorte. Fueran estudiados 97 lactantes no infectados y 33 lactantes infectados nacidos de madres infectadas con el VIH-1 en Belo Horizonte, Sureste de Brasil, de 1995 a 2003. El tiempo medio de seguimiento para los lactantes infectados y no infectados fue de 15,8 meses (variación: 6,8 a 18,0 meses) y 14,3 meses (variación: 6,3 a 18,6 meses), respectivamente. Se utilizó el modelo de regresión linear de efectos mixtos ajustado por máxima verosimilitud restringida para construir las curvas de crecimiento. RESULTADOS: Los z-escores PI, EI y PE de los lactantes infectados con el VIH-1 presentaron decrecimiento. A los seis meses, la diferencia promedio en los z-escores PI, EI y PE entre lactantes infectados y no infectados con el VIH era, respectivamente, 1,02, 0,59 y 0,63 desviaciones-estándares. A los 12 meses, la diferencia promedio en los z-escores PI, EI y PE entre lactantes infectados y no infectados era, respectivamente, 1,15, 1,01 y 0,87 desviaciones-estándares. CONCLUSIONES: El comprometimiento precoz y creciente de los indicadores antropométricos de niños infectados con el VIH-1 muestra la importancia de identificar precozmente niños infectados con el VIH que están en riesgo nutricional y la necesidad de evaluarse continuamente las intervenciones nutricionales adoptadas.

Longitudinal anthropometric assessment of infants born to HIV-1-infected mothers, Belo Horizonte, Southeastern Brazil.

OBJECTIVE: To evaluate the growth parameters in infants who were born to HIV-1-infected mothers. METHODS: The study was a longitudinal evaluation of the z-scores for the weight-for-age (WAZ), weight-for-length (WLZ) and length-for-age (LAZ) data collected from a cohort. A total of 97 non-infected and 33 HIV-infected infants born to HIV-1-infected mothers in Belo Horizonte, Southeastern Brazil, between 1995 and 2003 was studied. The average follow-up period for the infected and non-infected children was 15.8 months (variation: 6.8 to 18.0 months) and 14.3 months (variation: 6.3 to 18.6 months), respectively. A mixed-effects linear regression model was used and was fitted using a restricted maximum likelihood. RESULTS: There was an observed decrease over time in the WAZ, LAZ and WLZ among the infected infants. At six months of age, the mean differences in the WAZ, LAZ and WLZ between the HIV-infected and non-infected infants were 1.02, 0.59, and 0.63 standard deviations, respectively. At 12 months, the mean differences in the WAZ, LAZ and WLZ between the HIV-infected and non-infected infants were 1.15, 1.01, and 0.87 standard deviations, respectively. CONCLUSIONS: The precocious and increasing deterioration of the HIV-infected infants' anthropometric indicators demonstrates the importance of the early identification of HIV-infected infants who are at nutritional risk and the importance of the continuous assessment of nutritional interventions for these infants.

Impacto da terapia antirretroviral combinada no crescimento e nas taxas de hospitalização de crianças infectadas pelo HIV / Impact of HAART on growth and hospitalization rates among HIV-infected children

OBJETIVO: Avaliar mudanças em parâmetros de crescimento e hospitalização em crianças infectadas pelo vírus da imunodeficiência humana (human immunodeficiency virus, HIV) em uso de terapia antirretroviral combinada. MÉTODOS: As crianças foram avaliadas durante os primeiros 3 anos de terapia. A resposta clínica foi avaliada a cada 24 semanas com base em escores z de peso/idade e altura/idade. Modelos de regressão linear foram utilizados para identificar preditores de resposta clínica. Dados relevantes relativos à hospitalização dos pacientes foram obtidos retrospectivamente mediante revisão dos prontuários clínicos. RESULTADOS: Um total de 196 crianças foram avaliadas. A média do escore z aumentou de -1,62 (±1,32) no início do estudo para -1,14 (±1,12) na semana 24. A média do escore z de altura/idade aumentou de -1,88 (±1,45) para -1,66 (±1,18). Foi observada associação entre maiores escores z no início do estudo e maiores aumentos nos escores z de peso/idade ao longo do tempo. Cargas virais mais baixas e escores de altura/idade mais altos também estiveram associados com maior recuperação do crescimento. Oitenta e cinco crianças (43,3 por cento) foram hospitalizadas. A maioria das internações esteve associada a causas infecciosas, sendo apenas dois casos de infecções oportunistas. CONCLUSÃO: A terapia combinada resultou em aumentos significativos nos escores z de peso/idade e altura/idade. A menor idade, o uso de inibidores de protease e a classificação clínica em estágios avançados estiveram associados a uma maior efetividade do tratamento. Além disso, o estudo demonstrou a eficácia da terapia para a redução das taxas de hospitalização, morte e incidência de infecções oportunistas entre crianças portadoras do HIV.

OBJECTIVE: To evaluate HAART-associated changes in growth and hospitalization rates over time in a cohort of HIV-infected children. METHODS: Children starting HAART were assessed during the first 3 years of therapy. Clinical response was assessed every 24 weeks by z scores of weight-for-age and height-for-age. Linear regression models were used to detect predictors of clinical response. Pertinent information on hospitalizations was obtained retrospectively through review of medical records. RESULTS: A total of 196 children were assessed. Mean weight z score increased from -1.62 (±1.32) at baseline to -1.14 (±1.12) by week 24. Mean height z score increased from -1.88 (±1.45) at baseline to -1.66 (±1.18). Better z scores at baseline were associated with greater increases in weight z scores over time. Lower viral load and higher height z scores at baseline were also associated with improved height catch-up. Eighty-five children (43.3 percent) were hospitalized. Most hospitalizations were prompted by infectious disease, with only two due to opportunistic infections. CONCLUSION: HAART was associated with significant increases in weight and height z scores. Younger age, the use of protease inhibitors and advanced clinical disease were associated with better outcomes. The present study demonstrated the effectiveness of HAART in significantly reducing hospitalization, death, and incidence of opportunistic infections among HIV-infected children.