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Id: lil-772890
Autor: Tonami, Camila Alves.
Título: Avaliação do perfil de mutações e resistência aos inibidores de transcriptase reversa e protease em pacientes pediátricos infectados pelo HIV-1 / Avaliation of the profile of mutations and genotypic resistance to the nucleoside reverse transcriptase inhibotors.
Fonte: Botucatu; s.n; 2014. 60 p. ilus, tab.
Idioma: pt.
Tese: Apresentada a Universidade Estadual Paulista para obtenção do grau de Mestre.
Resumo: Apesar dos grandes avanços que conduziram a um declínio da infecção pelo HIV em crianças, a terapêutica antirretroviral vem sendo limitada pela emergência de resistência. Neste contexto, a finalidade deste estudo foi avaliar o perfil de mutações e resistência aos inibidores de transcriptase reversa análogos de nucleosídeos (ITRN) e não análogos de nucleosídeos (ITRNN) protease (IP) das variantes virais circulantes em pacientes pediátricos atendidos no Ambulatório de Imunologia Pediátrica da Faculdade de Medicina de Botucatu, UNESP. Foram avaliados dezenove pacientes, sendo dezesseis com falha terapêutica e, três virgens de tratamento. RNA viral plasmático foi utilizado como fonte para genotipagem das regiões genômicas da transcriptase reversa (TR) e protease (PR) do HIV. Os resultados demonstraram prevalência do subtipo B (78,95%). As mutações de resistência aos ITRNs encontradas em maior frequência foram L214F (73,7%), M184V (42,1%), R211K (42,1%), M41L (31,5%), T215Y (31,5%), L210W (21%), V118I (21%). As mutações K103N e Y188L encontradas em 26,3% e 10,5% dos pacientes foram as mais freqüentes entre as mutações associadas ao uso dos ITRNNs. Quanto aos IPs as mutações mais frequentes foram M36I (63,1%), L63P (52,6%), E35D (47,3%), R41K (31,5%), I13V (31,5%), M46V (26,3%), L90M (26,3%), I93L (26,3%), V77I (26,3%), V82A (21,1%), I54V (21,1%). No que se relaciona ao perfil de resistência, 3TC, AZT, EFV e NVP foram os ITR com menor potencial de uso devido à resistência. Já os IPs apresentam grande potencial de utilização na população estudada, o que se justifica pela alta barreira genética destes medicamentos. Dos três pacientes não tratados, um apresentava resistência a EFV e NVP, sugerindo ocorrência de resistência transmitida...

Although great progresses lead a decline of the HIV infection in children, the antiretroviral therapy has found obstacles as the resistance emergency. In this context the goal of this study was evaluate to the profile of mutations and genotypic resistance to the Nucleoside Reverse Transcriptase Inhibitors (NRTI), Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI) and Protease Inhibitors (PI) in children assisted in the Pediatric Immunology Ambulatory, Botucatu School of Medicine. Patients (19) were evaluated (16 with therapeutic failure and 3 naïve). Viral RNA was used as source to RT and PR genomic regions genotyping. Subtype B was the most frequent (78.95%) in thi study. The NRTI resistance mutations found were L214F (73.7%), M184V (42.1%), R211K (42.1%), M41L (31.5%), T215Y (31.5%), L210W (21%), V118I (21%). K103N and Y188L were found in 26.3% e 10.5% and we are associated with NNRTI use. About the PI the mutations most frequent were M36I (63.1%), L63P (52.6%), E35D (47.3%), R41K (31.5%), I13V (31.5%), M46V (26.3%), L90M (26.3%), I93L (26.3%), V77I (26.3%), V82A (21.1%), I54V (21.1%). The ARVs resistance analysis showed that 3TC, AZT, EFV and NVP have the lower potential for use due to resistance. PI presented great potential for use due to high genetic barrier. From three naïve patients one presented resistant viral variants to EFV and NVP, suggesting transmitted resistance...
Descritores: Antirretrovirais
Transcriptase Reversa do HIV
HIV-1
Limites: Humanos
Masculino
Feminino
Criança
Responsável: BR33.1 - Divisão Técnica de Biblioteca e Documentação


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Id: lil-772881
Autor: Tonami, Camila Alves.
Título: Avaliação do perfil de mutações e resistência aos inibidores de transcriptase reversa e protease em pacientes pediátricos infectados pelo HIV-1 / Avaliation of the profile of mutations and genotypic resistance to the nucleoside reverse transcriptase inhibotors.
Fonte: Botucatu; s.n; 2014. 60 p. ilus, tab.
Idioma: pt.
Tese: Apresentada a Universidade Estadual Paulista para obtenção do grau de Mestre.
Resumo: Apesar dos grandes avanços que conduziram a um declínio da infecção pelo HIV em crianças, a terapêutica antirretroviral vem sendo limitada pela emergência de resistência. Neste contexto, a finalidade deste estudo foi avaliar o perfil de mutações e resistência aos inibidores de transcriptase reversa análogos de nucleosídeos (ITRN) e não análogos de nucleosídeos (ITRNN) protease (IP) das variantes virais circulantes em pacientes pediátricos atendidos no Ambulatório de Imunologia Pediátrica da Faculdade de Medicina de Botucatu, UNESP. Foram avaliados dezenove pacientes, sendo dezesseis com falha terapêutica e, três virgens de tratamento. RNA viral plasmático foi utilizado como fonte para genotipagem das regiões genômicas da transcriptase reversa (TR) e protease (PR) do HIV. Os resultados demonstraram prevalência do subtipo B (78,95%). As mutações de resistência aos ITRNs encontradas em maior frequência foram L214F (73,7%), M184V (42,1%), R211K (42,1%), M41L (31,5%), T215Y (31,5%), L210W (21%), V118I (21%). As mutações K103N e Y188L encontradas em 26,3% e 10,5% dos pacientes foram as mais freqüentes entre as mutações associadas ao uso dos ITRNNs. Quanto aos IPs as mutações mais frequentes foram M36I (63,1%), L63P (52,6%), E35D (47,3%), R41K (31,5%), I13V (31,5%), M46V (26,3%), L90M (26,3%), I93L (26,3%), V77I (26,3%), V82A (21,1%), I54V (21,1%). No que se relaciona ao perfil de resistência, 3TC, AZT, EFV e NVP foram os ITR com menor potencial de uso devido à resistência. Já os IPs apresentam grande potencial de utilização na população estudada, o que se justifica pela alta barreira genética destes medicamentos. Dos três pacientes não tratados, um apresentava resistência a EFV e NVP, sugerindo ocorrência de resistência transmitida...

Although great progresses lead a decline of the HIV infection in children, the antiretroviral therapy has found obstacles as the resistance emergency. In this context the goal of this study was evaluate to the profile of mutations and genotypic resistance to the Nucleoside Reverse Transcriptase Inhibitors (NRTI), Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI) and Protease Inhibitors (PI) in children assisted in the Pediatric Immunology Ambulatory, Botucatu School of Medicine. Patients (19) were evaluated (16 with therapeutic failure and 3 naïve). Viral RNA was used as source to RT and PR genomic regions genotyping. Subtype B was the most frequent (78.95%) in thi study. The NRTI resistance mutations found were L214F (73.7%), M184V (42.1%), R211K (42.1%), M41L (31.5%), T215Y (31.5%), L210W (21%), V118I (21%). K103N and Y188L were found in 26.3% e 10.5% and we are associated with NNRTI use. About the PI the mutations most frequent were M36I (63.1%), L63P (52.6%), E35D (47.3%), R41K (31.5%), I13V (31.5%), M46V (26.3%), L90M (26.3%), I93L (26.3%), V77I (26.3%), V82A (21.1%), I54V (21.1%). The ARVs resistance analysis showed that 3TC, AZT, EFV and NVP have the lower potential for use due to resistance. PI presented great potential for use due to high genetic barrier. From three naïve patients one presented resistant viral variants to EFV and NVP, suggesting transmitted resistance...
Descritores: Antirretrovirais
Transcriptase Reversa do HIV
HIV-1
Limites: Humanos
Masculino
Feminino
Criança
Responsável: BR33.1 - Divisão Técnica de Biblioteca e Documentação


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Id: lil-764593
Autor: Santos, Lucianna Helene; Ferreira, Rafaela Salgado; Caffarena, Ernesto Raúl.
Título: Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors
Fonte: Mem. Inst. Oswaldo Cruz;110(7):847-864, Nov. 2015. graf.
Idioma: en.
Projeto: CAPES.
Resumo: Reverse transcriptase (RT) is a multifunctional enzyme in the human immunodeficiency virus (HIV)-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs) and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.
Descritores: Fármacos Anti-HIV/química
Desenho Assistido por Computador
Desenho de Fármacos
Transcriptase Reversa do HIV/antagonistas & inibidores
HIV-1
Inibidores da Transcriptase Reversa/farmacologia
-Infecções por HIV/tratamento farmacológico
Transcriptase Reversa do HIV/química
HIV-1
Modelos Biológicos
Estrutura Molecular
Relação Quantitativa Estrutura-Atividade
Inibidores da Transcriptase Reversa/química
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Revisão
Responsável: BR1.1 - BIREME


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Id: lil-758454
Autor: Zallio, Verónica; Marconi, Luis; Parenti, Pablo; Agostini, Marcela; Lupo, Sergio.
Título: Impacto del tratamiento antirretroviral en la función sexual de mujeres con VIH / Impact of antiretroviral treatment on sexual function of HIV-infected women
Fonte: Rev. med. Rosario;81(1):19-23, ene.-abr. 2015. tab.
Idioma: es.
Resumo: Objetivo. Describir la función sexual de un grupo de mujeres con VIH bajo tratamiento antirretroviral. Evaluar si existe diferencia entre las tratadas con un esquema que contiene Inhibidores No Nucleósidos de la Transcriptasa Inversa (INNTI) y aquéllas que reciben Inhibidores de la Proteasa (IP). Material y métodos. Estudio descriptivo, transversal. Muestra: 92 pacientes mujeres con VIH bajo tratamiento antirretroviral, que son asistidas en el Instituto Centralizado de Asistencia e Investigación Clínica Integral (CAICI). Instrumento: Se les realizó una encuesta que consta de características demográficas, preguntas referidas al VIH y al The Female Sexual Function Index (FSFI). Análisis estadístico: se utilizó ANOVA, Kruskall-Wallis, Chi cuadrado, regresión logística y alpha de Cronbach. Resultados. Edad media: 42±10 años; 65% tenían pareja estable, siendo el 73% de estas sero-discordantes. La mayoría (45,7%) estaban en tratamiento antirretroviral por más de dos años, con una media de CD4 mayor a 500 cél/ml y el 90% con carga viral plasmática indetectable. El 64,1% presentaba otra enfermedad asociada, por lo que el 55,4% tomaba medicación concomitante. El 27,2% continuó con su actividad sexual luego del diagnóstico de VIH, pero el 26,1% nunca la retomó. La puntuación total alcanzada por medio del FSFI fue de 20,4±10,1 para las tratadas con IP y 20±10,6 para las tratadas con INNTI (p <0,005). Conclusiones. La muestra analizada presentó un puntaje compatible con disfunción sexual. No hubo diferencia estadísticamente significativa en la función sexual de las mujeres tratadas con IP y las tratadas con INNTI

Summary Objective: To describe the sexual function in a group of women with HIV on antiretroviral treatment. To assess whether there is a difference between those treated with Non-nucleoside Inhibitors of he Reverse Transcriptase (NNRTI) and those receiving protease inhibitors (PIs). Material and methods: Descriptive, transversal study. Study sample: 92 women with HIV on antiretroviral therapy who are assisted in the Central Institute of Integral Assistance and Clinical Research (CAICI). Instrument: They completed a survey consisting of questions about demographic characteristics, HIV, and The Female Sexual Function Index (FSFI). Statistical analysis: ANOVA, Kruskal-Wallis, Chi-square, logistic regression and Cronbach's alpha. Results: Average age was 42±10 years; 65% had a steady partner, of which 73% were sero-discordant. Most patients (45.7%) had been on antiretroviral treatment for more than two years, with a mean CD4 greater than 500 cells/ml and 90% with undetectable plasma viral load. Other illnesses were present in 64.1%, and 55.4% were taking concomitant medication. Sexual activity after HIV diagnosis was continued by 27.2%, while 26.1% never resumed it. The total score achieved by the FSFI was 20.4±10.1 among those treated with IP and 20.0±10.6 among those treated with NNRTI(p<0.005). Conclusions: The score in the present sample supports the existence of sexual dysfunction. There was no statistically significant difference in the sexual function of women treated with either PI or NNRTI
Descritores: HIV
Sexualidade
Resultado do Tratamento
-Doenças Autoimunes/prevenção & controle
Inibidores da Protease de HIV
Inibidores da Transcriptase Reversa/uso terapêutico
Transcriptase Reversa do HIV/uso terapêutico
Limites: Humanos
Feminino
Responsável: AR16.1 - Biblioteca


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Aleixo, Agdemir Waleria
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Id: lil-678287
Autor: Memorias do Instituto Oswaldo Cruz; Tupinambas, Unai; Duani, Helena; Martins, Ana Virginia Cunha; Aleixo, Agdemir Waleria; Greco, Dirceu Bartolomeu.
Título: Transmitted human immunodeficiency virus-1 drug resistance in a cohort of men who have sex with men in Belo Horizonte, Brazil - 1996-2012
Fonte: Mem. Inst. Oswaldo Cruz;108(4):470-475, jun. 2013. tab.
Idioma: en.
Resumo: The presence of transmitted human immunodeficiency virus (HIV)-1 drug-resistance (TDR) at the time of antiretroviral therapy initiation is associated with failure to achieve viral load (VL) suppression. Here, we report TDR surveillance in a specific population of men who have sex with men (MSM) in Belo Horizonte, Brazil. In this study, the rate of TDR was evaluated in 64 HIV-infected individuals from a cohort of MSM between 1996-June 2012. Fifty-four percent had a documented recent HIV infection, with a seroconversion time of less than 12 months. The median CD4+T lymphocyte count and VL were 531 cells/mm3and 17,746 copies/mL, respectively. Considering the surveillance drug resistance mutation criteria, nine (14.1%) patients presented TDR, of which three (4.7%), five (7.8%) and four (6.2%) had protease inhibitors, resistant against nucleos(t)ide transcriptase inhibitors and against non-nucleoside reverse-transcriptase inhibitors mutations, respectively. Two of the patients had multi-drug-resistant HIV-1. The most prevalent viral subtype was B (44, 68.8%), followed by subtype F (11, 17.2%). This study shows that TDR may vary according to the population studied and it may be higher in clusters of MSM.
Descritores: Fármacos Anti-HIV/uso terapêutico
Farmacorresistência Viral
Infecções por HIV/virologia
HIV-1
Homossexualidade Masculina
-Brasil
CDABBREVIATIONS AS TOPIC LYMPHOCYTE COUNT
Genótipo
Infecções por HIV/tratamento farmacológico
Transcriptase Reversa do HIV/genética
HIV-1
Mutação
Prevalência
RNA Viral
Carga Viral
Limites: Adulto
Humanos
Masculino
Pessoa de Meia-Idade
Adulto Jovem
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Brigido, Luís Fernando de Macedo
Teixeira, Jorge Juarez Vieira
Bertolini, Dennis Armando
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Id: lil-643952
Autor: Gaspareto, Karine Vieira; Mello, Flávia Myrian Martins de Almeida; Dias, José Ricardo Colleti; Meneguetti, Vera Alice Fernandes; Storti, Marta Evelyn Giansante; Ferreira, João Leandro de Paula; Lança, André Minhoto; Rodrigues, Rosângela; Brígido, Luis Fernando de Macedo; Teixeira, Jorge Juarez Vieira; Bertolini, Dennis Armando.
Título: Genetic diversity and primary resistance among HIV-1-positive patients from Maringá, Paraná, Brazil / Diversidade genética e resistência primária entre pacientes HIV-1-positivos de Maringá, Paraná, Brasil
Fonte: Rev. Inst. Med. Trop. Säo Paulo;54(4):207-213, July-Aug. 2012. ilus, graf, tab.
Idioma: en.
Resumo: The objective of this study is to identify subtypes of Human Immunodeficiency Virus type 1 (HIV-1) and to analyze the presence of mutations associated to antiretroviral resistance in the protease (PR) and reverse transcriptase (RT) regions from 48 HIV-1 positive treatment naïve patients from an outpatient clinic in Maringá, Paraná, Brazil. Sequencing was conducted using PR, partial RT and group-specific antigen gene (gag) nested PCR products from retrotranscribed RNA. Transmitted resistance was determined according to the Surveillance Drug Resistance Mutation List (SDRM) algorithm. Phylogenetic and SimPlot analysis of concatenated genetic segments classified sequences as subtype B 19/48 (39.6%), subtype C 12/48 (25%), subtype F 4/48 (8.3%), with 13/48 (27.1%) recombinant forms. Most recombinant forms were B mosaics (B/F 12.5%, B/C 10.4%), with one C/F (2.1%) and one complex B/C/F mosaic (2.1%). Low levels of transmitted resistance were found in this study, 2/48 (2.1% to NRTIs and 2.1% for PI). This preliminary data may subsidize the monitoring of the HIV evolution in the region.

O objetivo foi identificar subtipos do Vírus da Imunodeficiência Humana tipo-1 (HIV-1) e analisar a presença de mutações/polimorfismos nas regiões da protease (PR) e transcriptase reversa (TR) de 48 pacientes virgens de tratamento atendidos no município de Maringá, Paraná, Brasil. O sequenciamento foi conduzido usando produtos de nested PCR dos genes da PR, TR parcial e group-specific antigen gene (gag) de RNA retrotranscrito. A interpretação da resistência transmitida foi realizada segundo o algoritmo Surveillance Drug Resistance Mutation List (SDRM). As análises filogenética e SimPlot dos segmentos concatenados classificaram as sequências como subtipo B 19/48 (39,6%), subtipo C 12/48 (25%), subtipo F 4/48 (8,3%), com 13/48 (27,1%) formas recombinantes. A maioria das formas recombinantes era mosaicos B (B/F 12,5%, B/C 10,4%), com um C/F (2,1%) e um mosaico complexo B/C/F (2,1%). A prevalência de resistência transmitida foi de 4,2% (2,1% para ITRN e 2,1% para IP). Baixos níveis de resistência transmitida foram encontrados nesse estudo, 2/48 (2,1% para INTR e 2,1% para IP). Esses achados, embora preliminares, podem contribuir no monitoramento da epidemia de HIV na região.
Descritores: Farmacorresistência Viral/genética
Infecções por HIV/virologia
Protease de HIV/genética
Transcriptase Reversa do HIV/genética
HIV-1
Mutação/genética
-Sequência de Bases
CDABBREVIATIONS AS TOPIC-CDABDOMINAL NEOPLASMS RATIO
Genótipo
HIV-1
Dados de Sequência Molecular
Filogenia
Limites: Adolescente
Adulto
Feminino
Humanos
Masculino
Pessoa de Meia-Idade
Adulto Jovem
Responsável: BR1.1 - BIREME


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Brito, Ana Maria de
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Id: lil-626436
Autor: Cavalcanti, Ana Maria Salustiano; Brito, Ana Maria de; Salustiano, Daniela Medeiros; Lima, Kledoaldo Oliveira de; Silva, Sirleide Pereira da; Diaz, Ricardo Sobhie; Lacerda, Heloisa Ramos.
Título: Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco
Fonte: Mem. Inst. Oswaldo Cruz;107(4):450-457, June 2012.
Idioma: en.
Resumo: Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.
Descritores: Farmacorresistência Viral/genética
Infecções por HIV/virologia
Protease de HIV/genética
Transcriptase Reversa do HIV/genética
HIV-1
Mutação/genética
-Fármacos Anti-HIV/uso terapêutico
CDABBREVIATIONS AS TOPIC LYMPHOCYTE COUNT
Genótipo
Infecções por HIV/tratamento farmacológico
Infecções por HIV/epidemiologia
HIV-1
Prevalência
Inibidores de Proteases/uso terapêutico
RNA Viral/genética
Inibidores da Transcriptase Reversa/uso terapêutico
Fatores Socioeconômicos
População Urbana
Carga Viral
Limites: Adulto
Feminino
Humanos
Masculino
Pessoa de Meia-Idade
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-612968
Autor: Castillo, Juan; Arteaga, Griselda; Mendoza, Yaxelis; Martínez, Alexander A; Samaniego, Rigoberto; Estripeaut, Dora; Page, Kathleen R; Smith, Rebecca E; Sosa, Nestor; Pascale, Juan M.
Título: HIV transmitted drug resistance in adult and pediatric populations in Panama / Farmacorresistencia transmitida del VIH en poblaciones adultas y pediátricas en Panamá
Fonte: Rev. panam. salud pública = Pan am. j. public health;30(6), Dec. 2011. tab.
Idioma: en.
Resumo: Objetivo. Investigar la prevalencia de farmacorresistencia transmitida del VIH en adultos en Panamá mediante un estudio del umbral modificado de la Organización Mundial de la Salud (OMS) e investigar las tasas de resistencia inicial en lactantesseropositivos para el VIH en Panamá.Métodos. En el Instituto Conmemorativo Gorgas, en 47 adultos seropositivos al VIH se efectuó la genotipificación de las mutaciones asociadas con la farmacorresistencia transmitida en los genes de la transcriptasa inversa y la proteasa del VIH-1, según las directrices del estudio umbral de la OMS, modificadas para incluir a las personas ≤ 26 años de edad. Las tasas de prevalencia de las mutaciones farmacorresistentes contra tres clases de fármacos antirretroviral —inhibidores de la transcriptasa inversaanálogos de nucleósidos, inhibidores de la transcriptasa inversa no análogos de nucleósidos e inhibidores de la proteasa— se clasificaron en bajas (< 5,0%), moderadas (5,0%–15,0%) o altas (> 15,0%). También se llevó a cabo genotipificación y se calcularonlas tasas de prevalencia de las mutaciones causantes de farmacorresistencia en 25 lactantes.Resultados. En los adultos de Panamá la farmacorresistencia transmitida fue moderada: 6 de 47 adultos seropositivos para el VIH presentaron una o más mutacionesasociadas con farmacorresistencia transmitida. Las mutaciones farmacorresitentes de transmisión horizontal fueron moderadas para los inhibidores de la transcriptasainversa análogos de nucleósidos y los inhibidores de la transcriptasa inversa no análogos de nucleósidos, y bajas para los inhibidores de la proteasa. En Panamá la transmisiónvertical del VIH ha disminuido en el período 2002–2007, pero la prevalenciade la farmacorresistencia del VIH transmitida por vía vertical es moderada (12,0%) y está surgiendo como un problema debido a la cobertura antirretroviral incompletadurante el embarazo...

Objective. To investigate the prevalence of transmitted drug-resistant HIV among adults in Panama by using a modified World Health Organization Threshold Survey (WHO-TS) and to investigate rates of initial resistance among HIV-positive infants in Panama.Methods. At the Gorgas Memorial Institute, 47 HIV-positive adults were genotyped for mutations associated with transmitted drug resistance (TDR) in the reverse transcriptase andprotease genes of HIV-1, according to WHO-TS guidelines, modified to include patients ≤ 26 years old. Prevalence rates for drug-resistance mutations against three classes of antiretroviraldrugs—nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors—were calculated as low (< 5.0%), moderate (5.0%–15.0%), and high (> 15.0%). Twenty-five infant patients were also genotyped and prevalence rates for drug-resistance mutations were calculated. Results. TDR among Panamanian adults was moderate: 6 of 47 HIV-positive adultsshowed one or more mutations associated with TDR. Horizontal TDR mutations were moderate for NRTIs and NNRTIs and low for protease inhibitors. Vertical transmission of HIV inPanama has decreased for 2002–2007, but vertical HIV TDR prevalence is moderate (12.0%) and is emerging as a problem due to incomplete antiretroviral coverage in pregnancy. Conclusions. The prevalence of HIV TDR indicated by this study, combined with knownrates of HIV infection in Panama, suggests more extensive surveys are needed to identify risk factors associated with transmission of HIV drug resistance. Specific WHO-TS guidelines for monitoring vertical transmission of drug-resistant HIV should be established.
Descritores: Fármacos Anti-HIV/farmacologia
Farmacorresistência Viral
HIV-1
-Fármacos Anti-HIV/uso terapêutico
Farmacorresistência Viral/genética
Genes pol
Genótipo
Infecções por HIV/tratamento farmacológico
Infecções por HIV/epidemiologia
Infecções por HIV/transmissão
Infecções por HIV/virologia
Inibidores da Protease de HIV/farmacologia
Inibidores da Protease de HIV/uso terapêutico
Protease de HIV/genética
Transcriptase Reversa do HIV/genética
HIV-1
Transmissão Vertical de Doença Infecciosa
Prevalência
Panamá/epidemiologia
Complicações Infecciosas na Gravidez/virologia
Inibidores da Transcriptase Reversa/farmacologia
Inibidores da Transcriptase Reversa/uso terapêutico
Limites: Adolescente
Adulto
Feminino
Humanos
Lactente
Recém-Nascido
Masculino
Gravidez
Adulto Jovem
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-612963
Autor: Avila-Ríos, Santiago; Mejía-Villatoro, Carlos R; García-Morales, Claudia; Soto-Nava, Maribel; Escobar, Ingrid; Mendizabal, Ricardo; Girón, Amalia; García, Leticia; Reyes-Terán, Gustavo.
Título: Prevalence and patterns of HIV transmitted drug resistance in Guatemala / Prevalencia y patrones de farmacorresistencia transmitida del VIH en Guatemala
Fonte: Rev. panam. salud pública = Pan am. j. public health;30(6):641-648, Dec. 2011.
Idioma: en.
Resumo: Objective. To assess human immunodeficiency virus (HIV) diversity and the prevalence of transmitted drug resistance (TDR) in Guatemala. Methods. One hundred forty-five antiretroviral treatment-naïve patients referred to the Roosevelt Hospital in Guatemala City were enrolled from October 2010 to March 2011. Plasma HIV pol sequences were obtained and TDR was assessed with the Stanford algorithm and the World Health Organization (WHO) TDR surveillance mutation list. Results. HIV subtype B was highly prevalent in Guatemala (96.6%, 140/145), and a 2.8% (4/145) prevalence of BF1 recombinants and 0.7% (1/145) prevalence of subtype C viruses were found. TDR prevalence for the study period was 8.3% (12/145) with the Stanford database algorithm (score > 15) and the WHO TDR surveillance mutation list. Most TDR cases were associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) (83.3%, 10/12); a low prevalence of nucleoside reverse transcriptase inhibitors and protease inhibitors was observed in the cohort (< 1% for both families). Low selection of antiretroviral drug resistance mutations was found, except for NNRTI-associated mutations. Major NNRTI mutations such as K101E, K103N, and E138K showed higher frequencies than expected in ART-naïve populations. Higher literacy was associated with a greater risk of TDR (odds ratio 4.14, P = 0.0264). Conclusions. This study represents one of the first efforts to describe HIV diversity and TDR prevalence and trends in Guatemala. TDR prevalence in Guatemala was at the intermediate level. Most TDR cases were associated with NNRTIs. Further and continuous TDR surveillance is necessary to gain more in-depth knowledge about TDR spread and trends in Guatemala and to optimize treatment outcomes in the country.

Objetivo. Evaluar la diversidad del virus de la inmunodeficiencia humana (VIH) y la prevalencia de la farmacorresistencia transmitida en Guatemala. Métodos. Entre octubre del 2010 y marzo del 2011 se incluyeron en el estudio 145 pacientes no tratados anteriormente con antirretrovirales, derivados al Hospital Roosevelt en la Ciudad de Guatemala. Se obtuvieron las secuencias pol a partir del VIH plasmático y se evaluó la farmacorresistencia transmitida con el algoritmo de Stanford y la lista de mutaciones para la vigilancia de la farmacorresistencia transmitida de la Organización Mundial de la Salud (OMS). Resultados. El subtipo B del VIH fue sumamente prevalente en Guatemala (96,6%, 140/145), y se encontró una prevalencia de formas recombinantes BF1 de 2,8% (4/145) y una prevalencia del subtipo C del virus de 0,7% (1/145). La prevalencia de la farmacorresistencia transmitida durante el período de estudio fue de 8,3% (12/145) según el algoritmo de la base de datos de Stanford (puntuación > 15) y la lista de mutaciones para la vigilancia de la farmacorresistencia transmitida de la OMS. En la mayoría de los casos, la farmacorresistencia transmitida se asoció con los inhibidores de la transcriptasa inversa no análogos de nucleósidos (ITINN) (83,3%, 10/12); en la cohorte se observó una baja prevalencia asociada con los inhibidores de la transcriptasa inversa análogos de nucleósidos y con los inhibidores de la proteasa (< 1% para ambas familias de fármacos). Se encontró una baja selección de mutaciones causantes de farmacorresistencia debidas a los antirretrovirales, excepto en las mutaciones asociadas a los ITINN. Las mutaciones importantes relacionadas con los ITINN, como K101E, K103N y E138K, mostraron frecuencias más elevadas que las esperadas en las poblaciones vírgenes de tratamiento antirretroviral. En las personas con un nivel de escolaridad más elevado se encontró un mayor riesgo de farmacorresistencia transmitida (razón de posibilidades 4,14; P = 0,0264). Conclusiones. Este estudio representa uno de los primeros intentos de describir la diversidad del VIH, y la prevalencia de la farmacorresistencia transmitida y sus tendencias en Guatemala. La prevalencia de la farmacorresistencia transmitida en Guatemala presentó un nivel intermedio y en la mayoría de los casos se asoció con los ITINN. Se necesita una vigilancia más intensa y sostenida de la farmacorresistencia transmitida para conocer más exhaustivamente su grado de diseminación y sus tendencias en Guatemala, al igual que para optimizar los resultados del tratamiento antirretroviral en el país.
Descritores: Fármacos Anti-HIV/farmacologia
Farmacorresistência Viral
HIV-1
-Fármacos Anti-HIV/uso terapêutico
Farmacorresistência Viral/genética
Escolaridade
Genes pol
Genótipo
Guatemala/epidemiologia
Infecções por HIV/tratamento farmacológico
Infecções por HIV/epidemiologia
Infecções por HIV/virologia
Inibidores da Protease de HIV/farmacologia
Inibidores da Protease de HIV/uso terapêutico
Transcriptase Reversa do HIV/genética
HIV-1
Epidemiologia Molecular
Mutação de Sentido Incorreto
Mutação Puntual
Vigilância da População
Prevalência
Inibidores da Transcriptase Reversa/farmacologia
Inibidores da Transcriptase Reversa/uso terapêutico
Limites: Adulto
Feminino
Humanos
Masculino
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-576787
Autor: Angelis, Daniela Souza Araújo de; Tateno, Adriana Fumie; Diaz, Ricardo Sobhie; Succi, Regina Célia de Menezes; Pannuti, Claudio Sergio; Gouvea, Aida de Fátima Barbosa; Machado, Daisy Maria.
Título: HIV-1 drug resistance genotypic profiles in children with undetectable plasma viremia during antiretroviral therapy
Fonte: Braz. j. infect. dis;15(1):60-65, Jan.-Feb. 2011. ilus, tab.
Idioma: en.
Resumo: Treatment of HIV-1 infection with highly active antiretroviral therapy has led to sustained viral suppression in the plasma in a large number of children. However, studies have suggested that the integrated provirus in resting CD4+ T lymphocytes could be a source of reactivatable virus and maintain drug-resistant virus. We evaluated the resistance-related mutations in children receiving antiretroviral therapy with prolonged viral suppression. Thirty-two peripheral blood mononuclear cell samples from 16 children with viral loads that had been below detection limits for at least 12 months were obtained at two different time points and the DNAs sequenced. The median CD4 cell count was 1,016 cells/mm³ (347-2,588) and 938 cells/mm³ (440-3,038) at the first and second time points, respectively. The median follow-up time was 15 months (9-27). Six (37.5 percent) and seven (43.75 percent) of the 16 patients showed at least one NRTI-associated mutation in the first and second samples, respectively. Two out of 16 (12.5 percent) had an NNRTI-associated mutation at the first time point and three out of 16 (18.75 percent) at the second. In addition, 14 out of 16 (87.5 percent) had at least one PI-associated mutation at both time points. Despite plasma HIV-1 RNA suppression for at least 12 months, resistance-related mutations from previous antiretroviral failures could still be detected in archival virus. Furthermore, viral evolution occurred at the reverse transcriptase region in spite of viral suppression to levels below 400 copies/mL. Persistence of archival resistant virus may be relevant when considering future treatment options.
Descritores: Fármacos Anti-HIV/uso terapêutico
Farmacorresistência Viral/genética
Infecções por HIV/virologia
HIV-1
Mutação/genética
-CDABBREVIATIONS AS TOPIC LYMPHOCYTE COUNT
Seguimentos
Genótipo
Infecções por HIV/tratamento farmacológico
Infecções por HIV/genética
Transcriptase Reversa do HIV/genética
HIV-1
Leucócitos Mononucleares/virologia
Carga Viral
Viremia/virologia
Limites: Criança
Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME



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