Avaliação da sensibilidade aos inibidores de entrada do HIV-1 em pacientes em falha virológica à terapia antirretroviral e novos aos inibidores de entrada

• Ano de defesa: 2009
• Autor(a) principal: Silva, Cecília Salete Alencar [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: HIV/AIDS; Resistência primária; Falha terapêutica; Inibidores de entrada; Síndrome de Imunodeficiência Adquirida
• Link de acesso: https://repositorio.unifesp.br/handle/11600/9046

Introduction: The chance of using combination of drugs within Highly Active Antiretroviral Therapy (HAART) has been resulted in a dramatic fall in the mortality and morbidity caused by the Human Immunodeficiency Virus-1 (HIV-1). Nevertheless, over the past years, there was observed a selection of strains resistant to some of these drugs, and today constitutes a major obstacle for the control of the disease, this fact highlights the need for the development of new drugs for the continuity of care. Objective: The aim of this study was to analyze the frequency of primary resistance to drugs that inhibit binding or fusion as Enfuvertide (T20) and BMS 378806, in samples of HIV-1 positive patients undergoing antiretroviral therapy and presenting virological failure. Methods: This study included 100 HIV-1 positive patients attending the Outpatient department of the Centro de Referência para o tratamento da AIDS (CRTA), using antiretroviral drugs and that show virological failure and with a result of viral load equal or above than 5000 copies / mL. The patients responded a questionnaire and medical records were also analyzed. The proviral DNA was amplified and sequenced for the region of the envelope of HIV-1. Results: Of 100 samples analyzed, 87 (87%) were positive and 13 (13%) were negative to the proviral DNA of HIV-1. Among the positive samples 80 (92%) were sequenced. Of the 80 samples sequenced, 73 (91.25%) were classified as subtype B, 2 (2.5%) recombinant (B 1 / F and 1 BC) and 5 (6.25%) were subtype F. Regarding the coreceptors used by viruses, 56 (70%) samples were classified as CCR5 and 24 (30%) as CXCR4. Among the samples analyzed, 8 (10%) had mutations for the fusion inhibitor Enfuvertide (T20), being one of them classified according to the criteria of the Consensus of the International Society for AIDS and the others as cited previously in another works. For the inhibitor BMS 378806, 6 (7.5%) samples had mutations, with a frequency of 28,6% for the subtype B. Conclusion In this study was detected primary resistance to antiretroviral class entry inhibitors of HIV-1 and was observed the importance of establishing criteria for identification of strains resistant to Enfuvertide (T20) before indicate the testing of genotyping.