TAILIEUCHUNG - Báo cáo y học: " Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Retrovirology cung cấp cho các bạn kiến thức về ngành y đề tài: " Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy. | Lewis et al. Retrovirology 2010 7 21 http content 7 1 21 RETR0VIR0L0GY RESEARCH Open Access Response of a simian immunodeficiency virus SIVmac251 to raltegravir a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy 1 f 2f 1 3 3 2 Mark G Lewis Sandro Norelli Matt Collins Maria Letizia Barreca Nunzio Iraci Barbara Chirullo 1 1 4 I- z -5 2 Jake Yalley-Ogunro Jack Greenhouse Fausto Titti Enrico Garaci Andrea Savarino Abstract Background In this study we successfully created a new approach to ART in SIVmac251 infected nonhuman primates. This drug regimen is entirely based on drugs affecting the pre-integration stages of replication and consists of only two nucleotidic nucleosidic reverse transcriptase inhibitors Nt NRTIs and raltegravir a promising new drug belonging to the integrase strand transfer inhibitor INSTI class. Results In acutely infected human lymphoid CD4 T-cell lines MT-4 and CEMx174 SIVmac251 replication was efficiently inhibited by raltegravir which showed an EC90 in the low nanomolar range. This result was confirmed in primary macaque PBMCs and enriched CD4 T cell fractions. In vivo monotherapy with raltegravir for only ten days resulted in reproducible decreases in viral load in two different groups of animals. When emtricitabine FTC and tenofovir PMPA were added to treatment undetectable viral load was reached in two weeks and a parallel increase in CD4 counts was observed. In contrast the levels of proviral DNA did not change significantly during the treatment period thus showing persistence of this lentiviral reservoir during therapy. Conclusions In line with the high conservation of the three main amino acids Y143 Q148 and N155 responsible for raltegravir binding and molecular docking simulations showing similar binding modes of raltegravir at the SIVmac251 and HIV-1 IN active sites raltegravir is capable of inhibiting SIVmac251 replication both in .

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