Resistência genotípica do hiv-1 em crianças verticalmente infectadas antes do início da terapia antirretroviral e após a primeira falha terapêutica

Abstract

The combination of aggressive antiretroviral therapy with at least three ARV drugs in combination with at least two classes of drugs is recommended for the maximum viral suppression, preservation and / or restoration of immune function associated with minimal drug-related toxicity This work is part of a research project of the Maternal Child AIDS Group, School of Medicine, Federal University of Minas Gerais (Grupo de AIDS Materno Infantil da Faculdade de Medicina da Universidade Federal de Minas Gerais) and was conducted from January 2006 to December 2009. This is a descriptive observational study to evaluate the prevalence of antiretroviral resistance in children infected with HIV-1. It is presented in the model of article for publication in accordance with the recommendations of the Board of the PostGraduate Health Child and Adolescent School of Medicine, Federal University of Minas Gerais (Colegiado do Curso de Pós-Graduação em Saúde de Criança e do Adolescente da Faculdade de Medicina da Universidade Federal de Minas Gerais). Initially the first article aimed at the prevalence of genotypic resistance before starting antiretroviral treatment (ARV) - primary resistance and prevalence of subtypes of HIV in children vertically infected with HIV. 41 children were analyzed for resistance testing, the median age was 6.0 years (IQR 25% -75%: 3.9-9.2) and the median age of first clinical consultation was 3.84 years (IQR 25% - 75%: 1:23 to 6:11). The maternal ARV exposure during the prenatal period occurred in only 3 (7.3%) mothers. According to the WHO criteria, the primary resistance was present in 4 / 41 (9.8%) children. Subtype B was the most prevalent (63.4%). The detection of primary resistance in children supports the most recent recommendation of the Brazilian Guidelines: having resistance testing in all HIV-infected children before the start of ARV therapy, irrespective of age at the diagnosis or exposure to ARVs during prenatal care. The second article aimed to describe the prevalence of genotypic resistance after the first treatment failure in children infected with HIV-1 and evaluate the immunological, virological and clinical response after the exchange based on genotyping. 50 children underwent the genotyping after the first treatment failure, from January 2002 to December 2007. The children median age was 7.6 years (IQR 25% - 75%: 6.3-10.5), the median age of onset of the first ARV regimen was 2.2 years (IQR 25% -75%: 1.0-4.5). The median duration of exposure to ARVs was 11.5 years (IQR 25% -75%: 3.57-6.91). The ARV regimen in use was 2ITRN + 1 PI (62%), 2 NRTI (18%), 2 NRTIs + 1 NNRTI (18%) and 3 NRTIs (2.0%). Subtype B was the most prevalent (76%). The prevalence of mutations was high: 84% of patients had at least one TAM. The average TAM was 3 (IQR 25% -75%: 2-4) for all patients and was not different when compared with the previously used ARV regimen (p = 0.60). All patients had received at least one NNRTI mutation linked to this class of ARV and the K103N mutation was the most prevalent (71.4%). Nelfinavir was the most used IP (85%); D30N and L90M were present at 57.1% and 39.3%, respectively. There was a high prevalence of mutations in the first term of the ARV regimen. These data demonstrate the need to complete the early resistance test, allowing for a more effective second ARV regimen.