Pharmacokinetics, Safety and Efficacy of Maraviroc in Treatment-experienced Pediatric Patients Infected With CCR5-Tropic HIV-1.

BACKGROUND: Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5-tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced pediatric patients infected with R5 HIV-1 and support registration of maraviroc for pediatric use. METHODS: This is an open-label, 2-stage, age-stratified, noncomparative multicenter study. One-hundred and three participants were enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were determined by body surface area and optimized background therapy, based on drug interactions with maraviroc in adults. Dose adjustment and pharmacokinetic reevaluation occurred if the average concentrations (Cavg) at Week 2 were <100 ng/mL (Stage 1-dose finding). RESULTS: Data from the Week 48 analysis demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety and efficacy) achieved Cavg ≥100 ng/mL. Doses were identified that achieved similar concentration ranges to those seen in adults. The majority (90/103) received optimized background therapy containing potent cytochrome P450 3A inhibitors. Maraviroc was well tolerated and the safety and efficacy were comparable to those of adults. All cohorts had a mean decrease from baseline in HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and percentage were seen for all age groups. CONCLUSIONS: The maraviroc dosing strategy resulted in participants achieving the target Cavg, with exposure ranges similar to those observed in adults on approved doses. The safety and efficacy of maraviroc in this pediatric population were comparable to those seen in adults.

Projetos de vida de adultos jovens portadores de HIV por transmissão vertical: estudo exploratório com usuários de um ambulatório de infectologia / Life projects of young adults with HIV acquired by vertical transmission: an exploratory study with patients of an infectious diseases' outpatients department

Esta pesquisa teve o intuito de conhecer os projetos de vida de jovens adultos que convivem com o HIV/aids a partir da transmissão vertical, com relação a: estudo, trabalho e constituição familiar. Outro objetivo foi o de conhecer sua vivência no que diz respeito à assistência recebida. Como instrumentos, foram utilizados: questionário sociodemográfico e entrevista semiestruturada. Foram realizadas 16 entrevistas com jovens de idade entre 18 e 22 anos, usuários de um ambulatório de um hospital público especializado na área de Infectologia. O material obtido nas entrevistas foi analisado segundo os princípios da análise temática. Foram encontradas seis categorias temáticas: estudo e escolaridade; trabalho e emprego; sexualidade e constituição familiar; vivência de preconceito; adesão ao tratamento; acolhimento. Os entrevistados referiram que a escola é importante meio para a inserção social e para a conquista da autonomia. O trabalho foi apresentado como principal fonte de subsistência e de independência. O exercício da sexualidade foi marcado pela situação de existência do HIV, determinando cuidados especiais; quanto à conjugalidade, os projetos dos entrevistados são variados: união informal, casamento oficial, vida sem cônjuge. No que diz respeito à maternidade/paternidade, os projetos são marcadamente influenciados pela portabilidade do HIV, despertando dúvidas e receios. Os entrevistados relataram a existência do preconceito em vários contextos. Quanto à adesão ao tratamento, revelaram a existência tanto de dificuldades como de mecanismos criados para enfrentá-las. O acolhimento por parte de familiares, amigos e profissionais da saúde foi considerado fundamental para o desenvolvimento e a manutenção de seus projetos de vida.

[The sexuality of HIV-positive adolescents: rights and challenges for healthcare]. / A sexualidade de adolescentes vivendo com HIV: direitos e desafios para o cuidado.

Sexuality and reproductive healthcare represent relevant issues for comprehensive care of HIV-positive adolescents. However, public policies and health services give this issue insufficient attention. The scope of this article is to assess how HIV-positive young people and teenagers cope with their sexuality, dating and the urge to have children and start a family. In a qualitative study, in-depth interviews were staged with 21 HIV-positive (contracted by vertical, sexual or intravenous transmission) teenagers and 13 caregivers of children and youths living in Sao Paulo and Santos. The interviews revealed the different ways teenagers cope with their sexuality and with the anxiety of HIV disclosure in this context. Lack of information about HIV prevention, lack of support and skills to cope with their sexuality were revealed in the reports. Furthermore, stigma and discrimination were the most frequently reported difficulties. The main challenges to be faced in Brazil in regard to this issue are discussed, especially the need to consider HIV-positive youth as entitled to sexual rights. Recommendations are also made for incorporating the issue into a humanized and comprehensive care approach for HIV-positive children and young people.

A sexualidade de adolescentes vivendo com HIV: direitos e desafios para o cuidado / The sexuality of HIV-positive adolescents: rights and challenges for healthcare

Sexualidade e saúde reprodutiva configuram questões relevantes para o cuidado integral à saúde de pessoas vivendo com HIV. Políticas públicas e serviços de saúde, entretanto, têm dedicado insuficiente atenção ao assunto. O objetivo deste trabalho é compreender como adolescentes e jovens soropositivos lidam com suas experiências sexuais e projetos de namoro, desejo de constituir família e de ter filhos. O estudo qualitativo entrevistou em profundidade 21 adolescentes vivendo com HIV (por transmissão vertical, sexual ou sanguínea) e 13 cuidadores de crianças e jovens, vivendo em São Paulo e em Santos, Brasil. As narrativas descrevem como aprenderam a lidar com a sexualidade e a ansiedade da revelação do diagnóstico nesse contexto. Destacam-se nas narrativas o despreparo, a desinformação sobre prevenção e a falta de apoio para lidar com a situação, assim como o estigma e a discriminação que atravessa grande parte das dificuldades relatadas. O artigo discute criticamente alguns dos desafios postos para uma adequada atenção à questão no Brasil, especialmente a consideração de jovens soropositivos como sujeitos de direitos sexuais, sugerindo diretrizes para a incorporação desta temática a um cuidado integral e humanizado de crianças e jovens vivendo com HIV.

Sexuality and reproductive healthcare represent relevant issues for comprehensive care of HIV-positive adolescents. However, public policies and health services give this issue insufficient attention. The scope of this article is to assess how HIV-positive young people and teenagers cope with their sexuality, dating and the urge to have children and start a family. In a qualitative study, in-depth interviews were staged with 21 HIV-positive (contracted by vertical, sexual or intravenous transmission) teenagers and 13 caregivers of children and youths living in Sao Paulo and Santos. The interviews revealed the different ways teenagers cope with their sexuality and with the anxiety of HIV disclosure in this context. Lack of information about HIV prevention, lack of support and skills to cope with their sexuality were revealed in the reports. Furthermore, stigma and discrimination were the most frequently reported difficulties. The main challenges to be faced in Brazil in regard to this issue are discussed, especially the need to consider HIV-positive youth as entitled to sexual rights. Recommendations are also made for incorporating the issue into a humanized and comprehensive care approach for HIV-positive children and young people.

Impact of macrolide therapy on mortality of HIV-infected patients with community-acquired pneumonia in a tertiary teaching hospital.

BACKGROUND: Bacterial pneumonia is one of the main causes of morbidity and mortality in patients infected by the human immunodeficiency virus (HIV). The main objective of this study was to evaluate the effect of macrolide therapy in combination with a beta-lactam based empiric regimen for inpatients with community-acquired pneumonia and HIV. METHODS: This is a retrospective cohort study of hospitalized patients. Adult patients who had received treatment with ceftriaxone or ceftriaxone plus clarithromycin were included. RESULTS: 76 patients met the inclusion criteria. Among baseline characteristics analyzed, only respiratory rate showed significant difference: patients who had received clarithromycin were more likely to have a respiratory rate > 30/min than patients who received only ceftriaxone (64% versus 36%, p = 0.03). ICU admission was the only outcome that showed a significant difference, more frequent in the ceftriaxone plus clarithromycin group (45% versus 20%, p = 0.03). CONCLUSIONS: This study does not support the addition of a macrolide to a beta-lactam based regimen in HIV-infected patients. This is probably related to the patients' immunodeficiency status, which impairs the immunomodulatory properties of the macrolides.

Impact of macrolide therapy on mortality of HIV-infected patients with community-acquired pneumonia in a tertiary teaching hospital

BACKGROUND: Bacterial pneumonia is one of the main causes of morbidity and mortality in patients infected by the human immunodeficiency virus (HIV). The main objective of this study was to evaluate the effect of macrolide therapy in combination with a beta-lactam based empiric regimen for inpatients with community-acquired pneumonia and HIV. METHODS: This is a retrospective cohort study of hospitalized patients. Adult patients who had received treatment with ceftriaxone or ceftriaxone plus clarithromycin were included. RESULTS: 76 patients met the inclusion criteria. Among baseline characteristics analyzed, only respiratory rate showed significant difference: patients who had received clarithromycin were more likely to have a respiratory rate > 30/min than patients who received only ceftriaxone (64 percent versus 36 percent, p = 0.03). ICU admission was the only outcome that showed a significant difference, more frequent in the ceftriaxone plus clarithromycin group (45 percent versus 20 percent, p = 0.03). CONCLUSIONS: This study does not support the addition of a macrolide to a beta-lactam based regimen in HIV-infected patients. This is probably related to the patients' immunodeficiency status, which impairs the immunomodulatory properties of the macrolides.

Improving survival in children with AIDS in Brazil: results of the second national study, 1999-2002 / Ampliação da sobrevida em crianças com AIDS no Brasil: resultados do segundo estudo nacional de 1999 a 2002

The objective of this study is to characterize survival in children with AIDS diagnosed in Brazil between 1999-2002, compared with the first national study (1983-1998). This national retrospective cohort study examined a representative sample of Brazilian children exposed to HIV from mother-to-child transmission and followed through 2007. The survival probability after 60 months was analyzed by sex, year of birth and death, clinical classification, use of antiretroviral therapy (ART) and prophylaxis for opportunistic diseases. 920 children were included. The survival probability increased: comparing cases diagnosed before 1988 with those diagnosed from 2001-2002 it increased by 3.5-fold (from 25 percent to 86.3 percent). Use of ART, initial clinical classification, and final classification were significant (p < 0.001) predictors of survival. Issues regarding quality of records and care were identified. The results point to the success of the Brazilian policy of providing ART. The improvement of clinical status contributes to quality of life, while indicating challenges, particularly practices to improve long-term care.

Este estudo caracteriza a sobrevida em crianças com AIDS no Brasil entre 1999-2002, contextualizando com o primeiro estudo nacional (1983-1998). Trata-se de coorte histórica, com crianças expostas ao HIV por transmissão vertical e acompanhadas até 2007. A probabilidade de sobrevivência em 60 meses foi analisada segundo sexo, ano de nascimento e de óbito, classificação clínica, uso de terapia antirretroviral (TARV) e de profilaxia para doenças oportunistas. No total, 920 crianças foram incluídas. A probabilidade de sobrevivência foi ampliada 3,5 vezes nos dois períodos avaliados, passando de 25 por cento antes de 1988 para 86,3 por cento no período de 2001-2002. Uso de TARV, classificação clínica inicial e atual/final foram preditores que influíram significativamente (p < 0,001) para a ampliação da sobrevida. Os resultados deste estudo indicam o sucesso da política brasileira para a abordagem das crianças infectadas com HIV. A melhora do estado clínico contribuiu para melhora da qualidade de vida, mas sinaliza-se para a necessidade de incorporação de práticas pautadas na integralidade do cuidado.

Efficacy, safety and tolerability of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatric patients. DESIGN: Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses including an optimized background regimen. METHODS: HIV-1-infected patients (2-18 years) with plasma viral load 1500 copies/ml or more were randomized to TPV/r 290/115 or 375/150 mg/m twice-daily oral solution and optimized background regimen. Week 48 efficacy, safety and tolerability results were evaluated. RESULTS: Children (n = 115; 97% treatment experienced) were randomized to low or high dose therapy. Eighty-eight remained on-treatment through 48 weeks. Baseline characteristics were similar between dose groups. At study entry, half of the HIV-1 isolates were resistant to all protease inhibitors. At 48 weeks, 39.7% low-dose and 45.6% high-dose TPV/r recipients had viral load less than 400 copies/ml and 34.5 and 35.1%, respectively, achieved viral load less than 50 copies/ml. Vomiting, cough and diarrhea were the most frequent adverse events. Grade 3 alanine aminotransferase elevations were observed in 6.3% of patients. No grade 4 alanine aminotransferase or grade 3/4 aspartate aminotransferase elevations were reported. CONCLUSIONS: TPV/r achieved a sustained virologic response, showed a good safety profile and was well tolerated at either dose. In pediatric patients with high baseline resistance profiles, high-dose TPV/r tended to demonstrate a better sustained response.

A supressao do Aleitamento materno e o HIV / Breast feeding suppression and HIV

O crescimento da epidemia de AIDS entre as mulheres levou, consequentemente, ao aumento do numero de casos em criancas, pois a grande maioria e devido a transmissao vertical do hiv, cuja probalidade de ocorrencia foi demonstrada em varios estudos. Foi evidenciado que a maioria dos casos, cerca de 65 porcento, ocorre durante o trabalho de parto e no parto propriamente dito e os 35 porcento restantes ocorrem intra-utero, principalmente nas ultimas semanas de gestacao; o aleitamento materno representa risco adicional de transmissao de 7 porcento a 22 porcento. A evidencia de transmissao do HIV pela amamentacao levou o Ministerio da Saude a contra-indicar o aleitamento materno por mulheres portadoras do HIV, assim como o aleitamento cruzado (feito por outra mulher). O presente artigo apresenta consideracoes sobre a utilizacao do teste rapido para pesquisa do HIV nas parturientes e sobre a importancia da supressao da lactacao nas mulheres HIV+, descrevendo os metodos que podem ser recomendados