Action of enfuvirtide on the pregnancy of albino rats ( Rattus norvegicus albinus, Rodentia, Mammalia ): biological assay and functional and histological analyses of exposed maternal-fetal organs

ABSTRACT Objective To assess the effects of enfuvirtide on pregnancy in albino rats and their fetuses. Methods Forty pregnant EPM 1 Wistar rats were randomly allocated into four groups: control (E) (distilled water twice/day), G1 (4mg/kg/day enfuvirtide), G2 (12mg/kg/day enfuvirtide), and G3 (36mg/kg/day enfuvirtide) groups. On the 20th day of gestation, the rats were anesthetized and subjected to cesarean section. Their blood was collected for laboratory analysis, and they were sacrificed. The offspring's fragments of their kidneys, liver, and placentas and the maternal rats' fragments of their lungs, kidneys, and liver were separated in the immediate postpartum period for light microscopy analysis. Results No maternal deaths occurred. In the second week at the end of pregnancy, the mean weight of the G3 Group was significantly lower than that of the G2 Group (p=0.029 and p=0.028, respectively). Analyzing blood laboratory parameters, the G1 Group had the lowest mean amylase level, and the G2 Group had the lowest mean hemoglobin level and the highest mean platelet count. In the morphological analysis, there were no changes in organs, such as the kidneys and liver, in both the maternal rats and offspring. Three maternal rats in the G3 Group had pulmonary inflammation in the lungs. Conclusion Enfuvirtide has no significant adverse effects on pregnancy, conceptual products, or functional alterations in maternal rats.

Acompanhamento farmacoterapêutico a pacientes usuários de enfuvirtida / Pharmaceutical care of patients treated with enfuvirtide

Enfuvirtida é um inibidor de fusão que interfere nascélulas com a penetração do vírus HIV. Sua aplicaçãoé feita por via subcutânea, o que provoca efeitos nocivos no local da aplicação. Os pacientes em uso deenfuvirtida deixam de usá-la constantemente, sugerindo uma baixa adesão devido às diferentes reações quepodem ocorrer com a administração subcutânea do medicamento. O objetivo da pesquisa, portanto, foi avaliar a relação entre a adesão e o acompanhamento farmacoterapêutico a pacientes usuários de enfuvirtida. A pesquisa foi realizada com pacientes com AIDS emuso de enfuvirtida, no CRE Metropolitano. Dados do perfil clínico e sócio-econômico foram coletados por meio de entrevistas. As entrevistas foram agendadas, mensalmente, para verificar a adesão do paciente ao uso de enfuvirtida durante os meses de setembro de 2008 a junho de 2009. Algumas peculiaridades do uso da forma farmacêutica injetável e a posologia de duas vezes por dia são identificadas como fatores limitantes para o tratamento. A maioria dos pacientes reconhece a importância do tratamento. Porém, cerca de 40%relatam dificuldades na aplicação e são intolerantes às reações adversas causadas pela aplicação subcutânea. Cerca de 33% deles, devido à assistência que estão recebendo, ainda esperam a liberação de novos medicamentos para a troca de esquema sem interrompero uso de enfuvirtida.

Enfuvirtide is a fusion inhibitor that interferes with the penetration of HIV into cells. It is injected subcutaneously, causing adverse side effects at the application site. Patients using enfuvirtide often discontinue the treatment, suggesting low compliance due to the various reactions provoked by the subcutaneous administration of the drug. The objective of this research was thus to assess the connection between pharmacotherapeutic follow-up and adherence of patients to the enfuvirtide regimen. The survey was conducted on AIDS patients prescribed enfuvirtide at a Metropolitan CRE (Brazilian Specialty Public Health Center). Data on the clinical profile and socioeconomic conditions were collected by interview. The interviews were scheduled monthly, to monitor patient adherence to the enfuvirtide treatment over the period from September 2008 to June 2009. Some peculiarities of the use of the injectable pharmaceutical form and the twice-daily injections are identified as limiting factors for the treatment. Most patients recognized its importance, but about 40% reported difficulties in injecting the drug and were intolerant of the adverse reactions caused by subcutaneous administration. About 33% of them, due to the accompaniment they are receiving, are still awaiting the release of new medicines so as to change their treatment plan without interrupting the use of enfuvirtide.

Enfuvirtida para o tratamento do paciente com aids: o divisor de águas / Enfuvirtide in the treatment of AIDS patient: the turning point

O estudo, realizado em um Hospital de Referência em Doenças Infecciosas do Ceará, de fevereiro de 2006 a fevereiro de 2007, visou identificar o perfil sociodemográfico dos usuários de Enfuvirtida e as principais dificuldades e facilidades encontradas por eles durante o tratamento anterior e o atual. A amostra inicial teve 23 pacientes; destes, 18 concordaram em participar. A análise descritiva dos dados quantitativos foi realizada pela distribuição de frequências e os dados qualitativos, submetidos à análise de conteúdo. Observou-se que 83 por cento eram do sexo masculino, 78 por cento eram solteiros e a maioria tinha entre 30 e 52 anos e em média oito anos e meio de tratamento antirretroviral. Dos dados qualitativos, emergiram as categorias (1) Tratamento anterior: dificuldades e adversidades e (2) Tratamento atual: da cognição à habilidade. As dificuldades dos tratamentos anteriores eram o tamanho e a quantidade elevada de comprimidos e aos efeitos colaterais; a facilidade apontada foi o fácil manejo da medicação. Quanto ao tratamento atual, as dificuldades foram a autoadministração e os nódulos nos locais de aplicação da Enfuvirtida e as facilidades, a ausência de efeitos gastrointestinais e melhora da carga viral. É importante implementar um trabalho interdisciplinar que ajude os pacientes a vencer as dificuldades no tratamento, além de trabalhos em grupos para melhor abordar as dificuldades e ajudar a aumentar a adesão à terapêutica.

The study was carried out in a Hospital of Reference in Infectious Diseases of Ceará, from February 2006 to February 2007, and and aimed at identifying the socio-demographic profile of Enfuvirtide users and their main difficulties/facilities in previous and current treatment scheme. The initial sample analyzed the medical record of 23 patients;18 agreed to participate, comprising the final sample. The descriptive analysis of quantitative data was carried out through the distribution of frequencies and quantitative data, submitted for content analysis. It was observed that 83 percent were male, 78 percent were single and the majority was between 30 and 52 years old and, in average, eight years and a half of antiretroviral treatment. From qualitative data, two categories emerged: (1) Previous treatment: difficulties and adversities and (2) Current treatment: from cognition to ability. The difficulties to conduct previous treatments were related to the size and high amount of tablets and side effects. As for facility, the easy drug administration was indicated. Regarding the current treatment, the difficulties were self administration and nodules on the sites where Enfuvirtide was applied and the facilities were absence of gastrointestinal effects and improvement of viral load. It's important to implement an interdisciplinary work that helps patients overcome the difficulties of the treatment, in addition to works in groups in order to better address the difficulties and help increase adhesion to treatment.

Enfuvirtide: el primer paso de una nueva estrategia de tratamiento antirretroviral / Enfuvirtide: the first step for a new strategy of antiretroviral therapy

Enfuvirtide (antes T-20) es el primer inhibidor de la entrada a la célula del HIV-1 en ser aprobado. Es un péptido análogo de la porción HR2 de la glucoproteína de superficie viral gp41. Su mecanismo de acción consiste en la unión competitiva a la porción HR1 de la gp41 para impedir los cambios conformacionales del complejo gp41-gp120 tras la unión del HIV-1 a los receptores celulares, impidiendo así el acercamiento y posterior fusión entre el virus y la célula. Se aplica por vía subcutánea. Los resultados de los principales estudios clínicos (TORO 1 y 2) llevados a cabo en pacientes con fallo virológico, tratamientos previos con antirretrovirales y portadores de cepas virales altamente resistentes, mostraron que quienes recibieron enfuvirtide + HAART optimizado, elegido mediante un test de resistencia, presentaron mayores beneficios que quienes sólo recibieron HAART optimizado, en términos de mejor recuperación inmune y mayor descenso de la carga viral de HIV. Los mejores resultados se observaron en el subgrupo de pacientes con más drogas útiles en el HAART según el test de resistencia, una menor carga viral de HIV y un mayor recuento de linfocitos CD4 basales. El principal efecto adverso es el desarrollo de lesiones por hipersensibilidad en los sitios de aplicación. El alto costo de enfuvirtide se vio compensado por una reducción en los costos de internación.

Enfuvirtide (T-20) is the first approved HIV-1 entry into cells' inhibitor. It is a peptide with an amino acid sequence analogue to HR2 region of the viral surface glycoprotein gp41. Its mechanism of action is the competitive binding to HR1 region of the gp41, preventing the interaction between HR1 and HR2 and impeding the conformational changes in gp41 necessary for fusion of the virus with the cell. Its application is by subcutaneous injection. The main clinical trials of enfuvirtide (TORO 1 and 2) were performed in HIV-infected patients with virological failure, high antiretroviral experience and highly resistant viral isolates. Those trials showed that the addition of enfuvirtide to an optimized HAART (chosen with a resistance test) provided better results than HAART alone, measured by drop in viral load and immunologic benefit. The best results were observed in the subgroup of patients with more useful drugs in HAART (according to the information of the resistance test), a lower viral load, and a higher CD4 cell count at baseline. The most important adverse event is the production of injection drug hypersensitivity reaction in 98% of patients. The high cost is compensated by a reduction in costs derived from admissions.

A prevalência de fatores de risco para baixa adesão na terapia com enfuvirtida, nos usuários soropositivos para o HIV em tratamento nos centros de referência em Porto Alegre - RS / The prevalence of risk factors for decreasing adhesion in the therapy with enfuvirtida in HIV infected users in treatment in centers of reference in Porto Alegre - RS

Introdução: Em 2005 o Ministério da Saúde do Brasil disponibilizou a enfuvirtida, o primeiro inibidor de fusão, uma nova classe de anti-retrovirais com ação extracelular. As dificuldades relatadas pelos primeiros usuários, em um dos centros de referência, e a carência de estudos envolvendo os usuários do Sistema Único de Saúde motivaram esta pesquisa. Objetivo: identificar os fatores de risco para baixa adesão ao tratamento com Enfuvirtida. Métodos: foram entrevistadas 37 pessoas de Porto Alegre, compreendendo a população total de usuários de enfuvirtida nesta cidade até o mês de outubro de 2006. Resultados: 27% dos pacientes já pensaram em desistir do tratamento, 22,2% referiram esquecimento de dose nos últimos 30 dias e 45,9% não souberam diferenciar HIV de aids. Os efeitos adversos locais ocorreram em todos os usuários, houve dor nos locais de aplicação em 81,1% dos casos, fato que não atrapalhou as atividades diárias (70,3%). Quanto às aplicações, 28,9% não tiveram a primeira dose supervisionada, 27% não realizaram massagem após as aplicações, 46% dos pacientes usavam regiões não orientadas pela enfermagem para aplicação, 29,7% acharam “difícil” encontrar um local para aplicar. Conclusão: o estudo reforça a necessidade do acompanhamento direto por um profissional de enfermagem para aplicação do medicamento, visto que os procedimentos podem parecer fáceis, mas requerem boa técnica para diluição, aspiração e aplicação a fim de diminuir os efeitos adversos locais, assim como as orientações sobre os cuidados após a aplicação.

Introduction: In 2005 the Ministry Health of Brazil provided Enfuvirtide, the first inhibitor of fusion, a new class of anti-retroviraes with extracellular action. The difficulties described by the first users, in one of the reference centers, and the lack of studies with the users of the Public Health Department, had motivated this research. Objective: to identify risk factors for low adhesion to the treatment with enfuvirtida. Methods: 37 people from Porto Alegre had been interviewed, the total population of users of enfuvirtide in this city until October, 2006. Results: had presented that 27% of the patients had already thought about giving up the treatment, 22,2% had forgotten to take the dose in the last 30 days and 45,9% do not know the difference between HIV and AIDS. The local adverse effect had occurred in all the users, pain in the application places were present in 81,1% of the cases, but it did not interfere in daily activities (70,3%). Concerning applications, 28,9% had not had a first supervised dose, 27% did not make a massage after the applications, 46% of the patients also used regions for application which were not guided by the nurses, 29,7% had had “difficulties” in finding a place to apply. Conclusion: the study strengthens the necessity of the direct accompaniment by a nursing professional, although the procedures can seem easy, they require good technique for dilution, aspiration and application to diminish the local adverse effects, as well as the orientation on the care after the application.