Navegando por Palavras-chave "Inibidores Da Integrase"

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    Prevalência de mutações de resistência aos antirretrovirais em pacientes com falha virológica em uso do raltegravir em regimes de terapia de resgate
    (Universidade Federal de São Paulo (UNIFESP), 2021) Nassar, Isabella Barbosa Pessoa [UNIFESP]; Diaz, Ricardo Sobhie [UNIFESP]; Universidade Federal de São Paulo
    The integrase enzyme is fundamental to the HIV virus replication process, being responsible for the integration of viral DNA into the host cell genome, andgenome and is therefore a potential target for rescue treatment among people living with HIV / AIDS. The understanding of infection and the quality of antiretroviral therapies (HAART) has been growing a lot in recent years, and the class of integrase inhibitors fits in this segment. Currently, two integrase inhibitors are in use in Brazil: raltegravir (RAL) and dolutegravir (DTG). Another three integrase inhibitors approved by the FDA and ANVISA, which have not yet arrived in Brazil, are elvitegravir, cabotegravir (CAB) in solution for injection and bictegravir (BIC), approved by ANVISA in Brazil. The low genetic barrier to RAL has favored the selection of three resistance pathways: Y43R / H / C, N155H / R and Q148H / K / R, the latter path causing cross resistance to dolutegravir. The aim of this work was to analyze the prevalence of resistance mutations to integrase inhibitors among patients with virological failure to rescue schemes containing raltegravir. To this end, 701 cases with RAL virological failure and current or previous virological failure to reverse transcriptase inhibitors similar tolike nuclei (t) ids, (ITRN) reverse transcriptase inhibitors not analogous to nuclei (t) ids were evaluated (ITRNN) and protease (IP) inhibitors. These data were collected from the Genotyping Examination Control System - SISGENO, and from the Lymphocyte Count Control System - CD4 + / CD8+ and HIV viral load - SISCEL, from January 2017 to December and 2018. From 701 patients 182 (26%) had resistance mutations to integrase inhibitors, 145 (20.7%) to IPs, 339 (48.4%) to NRTIs, and 327 (46.7%) to NRTIs and the interpretation of mutations of resistance were made by the IAS-USA algorithm. The isolated and prevalent mutations in rescue schemes containing RAL were N155H / S, and L74I / M, and among the associated mutations, the most prevalent was G140S + Q148H in 16 cases. We compared the median age, viral load and TCD4+ cells of patients with and without resistance mutations in integrase. The median age of patients with resistance mutations in to integrase was 41.0 years (p = 0.0008) with the majority being male 101 (55.5%) (p = 0.0017). The median viral load of patients with resistance mutations in integrase was 4.62 and LTCD4+ with resistance18 mutations of 171.5 (p <0.0001). When correlating viral load with the number of mutations, the results point to increase viral load in patients who had up to two mutations. However, with the presence of 3 or more mutations, the results do not show statistical significance. The patterns of resistance to integrase inhibitors (INIs) by subtype were also analyzed, with the majority having the integrase region of subtype B, followed by C and F1. In the general profile of the subtypes of the 701 genomic fragments, the most prevalent was subtype B with (74.04%) in the integrase region, followed by C with (15.41%) and F1 with (9.27%). In reverse transcriptase, subtype B with (72.90%), C (12.98%), F1 (11.13%). In protease B with (72.90%), C (12.98%) and F1 (11.13%). Loop V3 predominated B with (84.30%), C (9.87), F1 (5.83%). Gp41 B with (80%), followed by F1 with (15%) and C (5%). The longer time of exposure to rescue schemes containing RAL, revealed a higher prevalence of mutations in codon 148. In the identification of tropism, we observed that in the initial phase of HIV infection, mutational pathways 155 and 143 predominated, and in the advanced phase, via 140 and 148. When comparing the number of schemes with the number of mutations in integrase, our results demonstrate that the greater the number of accumulated mutations in integrase, the greater the number of schemes (p = 0.0007).