Avaliação do perfil de resistência genotípica do HIV-1 aos antirretrovirais em crianças e adolescentes em falha terapêutica em goiás, no período de 2003 a 2015

• Autor(a) principal: Albuquerque, Maly de
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/6713
• topic: HIV; Resistência a medicamentos; Genotipagem; Criança; Adolescente; Antirretroviral; HIV; Drug resistance; Genotype; Child; Adolescente; Anti-retroviral agentes; CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS

Objective: The aims of this study were to detect and identify drug resistance mutations through genotyping related to antiretroviral (ARV) resistance in children and adolescents infected with HIV-1 and with therapeutic failure. Methods: This was a descriptive study based on a retrospective cohort of HIV-infected children and adolescents diagnosed between 1992 and 2013. The pattern of ARV resistance mutations was analyzed in 65 children and adolescents, in therapeutic failure and followed up in a reference pediatric infectious disease clinic since diagnosis. A total of 92 genotypic resistance tests were carried out from 2003 to 2015. Genotypic tests were collected at the Central Laboratory (LACEN) and performed by the RENAGENO laboratory. For the interpretation of resistance the ARV algorithm was used (RENAGENO’s algorithm version 13th, 2015) and the Stanford’s algorithm (Stanford HIV drug resistance database, 2015). The study protocol’s was approved by the ethics committee of the HC / UFG and HDT / SES. Statistical analysis was performed with the software Microsoft Excel version 2010 and Statistical Package for the Social Sciences (SPSS®) 20.0 for Windows. Descriptive and inferential analyzes (t-Student and U-Mann-Whitney tests) were performed, considering the level of significance at 5%. Results: The sample consisted of 65 children and adolescents, with median age at diagnosis of 29.2 months (range from 2 months to 120 months); the majority was female (36/65). A total of 64 (98.5%) patients acquired HIV vertical transmission. Approximately 55% of the patients presented with severe immunosuppression at diagnosis of HIV, and 33% belonged to class B or C, according to the CDC-1994 clinical and immunological classification. The median baseline CD4 lymphocyte count was 921 cells/mm3. HIV viral load, before starting HAART, showed a median of 678,998 copies (log 5.83). At the time of first genotyping, CD4 ranged from 1 to 2940 cells/mm3, with a median of 608 cells/mm3, with a median of 40,548 copies/mL (log 4,60). Most mutations were found in the NRTI class (98.5%), followed by NNRTI (75.4%) and PI (44.6%). The most frequent mutations in the NRTI class were T215 codons (83.1%), with prevalence of T215YF (69.2%), M184V (69.3%), and M41L (52.3%). The most observed mutations in the NNRTI class were K103N / S (40.0%), 190A / S (30.8%), 101E / P / Q (23.1%). Mutations associated with resistance in protease occurred mainly in codons 54, 82 and 46, with rates of 35.4%; 32.3%; 27.7%; respectively. Resistance to more than one class occurred in 41.5%, 12.3% and 35.4% with the combination of NRTIs and NRTIs, ITRN + IP / r, and with the three NRTI + NRTI + IP classes respectively. After rescue therapy, approximately 90% of the patients analyzed had viral suppression, with HIV viral RNA levels below the detection limits (<50 or 40 copies) after 24 weeks of change in the combined antiretroviral regimen (P <0.001). Immunological response resulted in benefit, with significant elevation in CD4 + T cell count (P <0.001). Conclusions: Our study provided relevant information on the results of the genotypic resistance test after failure of long-term ARV therapy in children and adolescents infected with HIV. There were high mutation rates in all antiretroviral classes tested. Rescue therapy guided by the genotypic test provided high rates of viral suppression. Thus, the genotype test emphasizes the possibility of adequately composing an ARV regimen, with a high genetic barrier, using the new drugs and new classes of ARV drugs, with the objective of avoiding the therapeutic failure after rescue and preventing the accumulation of other mutations related to drug resistance.