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1.
Prensa méd. argent ; 105(3): 99-105, may 2019. tab
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1025198

RESUMO

Introducción: El tratamiento antirretroviral de alta eficacia (TARGA) ha desplazado a las infecciones oportunistas como principal causa de hospitalización en infectados por el HIV. Sin embargo, algunos autores hallaron que las causas de internación por HIV en Buenos Aires no cambiaron a pesar del acceso universal al TARGA desde 1996. Pacientes y Métodos. Para confirmar estos resultados revisamos todos los ingresos hospitalarios ocurridos durante tres años en un hospital general de la ciudad de Buenos Aires. Resultados: 57 pacientes (34 hombres) tuvieron 79 hospitalizaciones: 43 ingresaron sólo una vez y los 14 restantes tuvieron dos o más ingresos hasta totalizar 36 internaciones. La edad fue de 44.46 ± 11.55 años (promedio ± desvío estándard), 43 pacientes (75.45%) se sabían HIV + y 28 de ellos (65.12%) recibían TARGA al ingreso, 31 hospitalizaciones (39.24%) fueron causadas por enfermedades marcadoras de SIDA; 35 (44.30%) por infecciones no marcadoras de SIDA (INMS) y 13 (13.46%) por enfermedades no infecciosas. Tuberculosis fue el diagnóstico más frecuente (11 casos, 13.92%), seguida por meningitis a Cryptococcus neoformans en 9 (11.39%) y toxoplasmosis cerebral en 6 (7.59%). Entre las INMS, la neumonía fue la principal causa de hospitalización (13 pacientes, 16.46%). Discusión: Estos resultados confirman resultados previos comunicando que las causas de hospitalización en infectados por el HIV no cambiaron en respuesta al TARGA en Buenos Aires, lo que puede estar reflejando problemas de detección o adherencia, o puede estar relacionado con resistencia viral, razones sociales o cualquier combinación de estos factores (AU)


Introduction. High Active Antiretroviral Treatment (HAART) displaced opportunistic infections as the main cause of hospitalization in HIV infected patients. However, some authors found that causes for hospitalization in HiV infected patients did not changed at Buenos Aires although this country offers universal access to HAART since 1996. Patients and Methods. We analyzed all the HIV related admissions recorded during three years at a general hospital. Results. 57 patients (34 men) were hospitalized 79 times. 43 out of them were hospitalized only one time. The reaining 14 were hospitalized 36 times. Age was 44.46 ± 11.55 years (mean ± standard deviation). 43 patients (75.45%) had a previous diagnosis of HIV infection. 28 of them (65.12%) received HAART. 31 hospitalizations (39.24%) were caused by AIDS defining events. 35 (44.30%) related to non-AIDS-defining infections diseases (NADID), and 13 (13.46%) to non-infections diseases. Tuberculosis was the prevalent illness (11 cases, 13.92%), followed by cryptoccal meningitis in 9 (11.39%) and cerebral toxoplasmosis in 6 (7.59%). Among NADID, pneumonia was the main cause of admission (13 patientes, 16,46%). Discussion: These results confirm previous reports showing that causes of HIV related hospitalization remain unchanged in spite of HAART at Buenos Aires, which may be reflecting problems of detection and adherence, or may be related to local viral resistance, social reasons, or any combination of these factors (AU)


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Doenças Transmissíveis/diagnóstico , Análise Estatística , Estudos Retrospectivos , HIV/imunologia , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Farmacorresistência Viral/imunologia , Doenças não Transmissíveis , Pacientes Internados/estatística & dados numéricos
3.
Mem. Inst. Oswaldo Cruz ; 112(6): 411-418, June 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-841806

RESUMO

BACKGROUND The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. OBJECTIVE The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil. METHODS DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. Their genotype and drug-resistance mutations were identified using bioinformatics tools. Clinical and epidemiological data were analysed. FINDINGS Among 263 individuals (46.4% male), 97.5% were asymptomatic and 49.1% were receiving treatment. Most of the individuals were 31 to 40 years old (36.9%) and infected through heterosexual contact (40.7%). The predominant genotype was B (68.1%) followed by BF recombinants (18.6%). Among the individuals infected with either F or BF genotypes, 68.4% were women and 76.8% were infected through heterosexual transmission. The prevalence of associated mutations conferring antiretroviral resistance was 14.2%, with 3.8% of all mutations conferring resistance to protease inhibitors, 9.43% to nucleoside reverse transcriptase inhibitors, and 8.5% to non-nucleoside reverse transcriptase inhibitors. Drug resistance was higher in individuals receiving treatment (26.1%) than in the drug-naïve (4.3%) individuals. MAIN CONCLUSIONS This study will contribute to the understanding and monitoring of HIV epidemic in this Brazilian region.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/imunologia , Análise de Sequência de DNA , Farmacorresistência Viral/genética , Brasil/epidemiologia , Fatores de Risco , HIV-1 , Mutação/genética
4.
Fortaleza; s.n; 2016. 105 p. ilus, tab.
Tese em Português | LILACS | ID: biblio-971945

RESUMO

A terapia antirretroviraltemporobjetivodiminuiramorbidadeemortalidadedaspessoascomHIV/AIDS,melhorandoaqualidadeeaexpectativadevida. Paradoxalmente, o tratamento irregular pode favorecer a seleçãode variantes resistentes, representandouma das principais causas de falha terapêutica. Tais cepas resistentes podem ser transmitidas a outros indivíduos(resistência transmitida), predispondo àfalha precoce do tratamento inaugural. Ostestesderesistência,principalmenteagenotipagem,permitemadetecçãodemutaçõesdogenomaviral.OobjetivodesteestudofoicaracterizarasmutaçõesderesistênciatransmitidadoHIV-1aosantirretroviraisempacientesrecém-diagnosticadosnoCentro de Testagem e Aconselhamento (CTA) de Fortaleza.Duranteoperíododeoutubrode2013asetembrode2014,foramrecrutadospacientescomtestereagente para oHIVrealizadono CTA. Foram colhidas amostras para realizaçãode quantificação da cargaviral(AbbottRealTime),contagemdelinfócitos CD4+(FACSCaliburBD)egenotipagemHIV-1(TruGeneSiemens).As sequências genéticasforam alinhadas pelo programa MEGA eBioEdit. Ossubtipos do vírus HIV-1 foram determinados e identificados empregando análises no banco de dados do REGA HIV Subtyping Tool. A análisedas mutações de resistência aos antirretrovirais foi realizada utilizando o algoritmo da Universidade de Stanford(HIVdbProgram)e as mutaçõesderesistênciatransmitidaforamidentificadasempregandoaCalibraçãodeResistênciaPopulacional.Foram obtidas amostras biológicas de 108 pacientes, sendo que em 105delas foi possível realizar a reação de sequenciamentoea avaliação quantoàpresençademutaçõesderesistênciaassociadasaos antirretrovirais...


Antiretroviral therapy aims to reduce morbidity and mortality of people with HIV / AIDS, improving the quality and life expectancy. Paradoxically, the irregular treatment may favor the selection of resistant variants, representing a major cause of treatment failure. Such resistant strains can be transmitted to other individuals (transmitted resistance) predisposing to early failure of the inaugural treatment. Resistance tests, particularly genotyping, allow mutation detection in the viral genome. Theaim of this study was to characterize the transmitted resistance HIV-1 mutations to antiretroviral drugs in newly diagnosed patients in the Counseling and Testing Center (CTC) in Fortaleza. During the period October 2013 to September 2014, patients with reagent test for HIV were recruited at CTC. Samples for viral load quantitation (Abbott RealTime), CD4 lymphocytes count (BD FACSCalibur) and HIV-1 genotyping (TRUGENE Siemens), were collected. Genetic sequences were aligned by MEGA and BioEdit program. Thesubtypes of HIV-1 were determined and identified using analysis in REGA HIV subtyping Tool database. The analysis of the antiretroviral resistance mutation was performed using the algorithm of Stanford University (HIVdb Program) and transmitted mutation resistance was identified using the CalibratedPopulationResistance (CPR). Biological samples were obtained from 108 patients, among which in 105 was possible to perform the sequencing reaction and evaluation for the presence of mutations to conferantiretroviral drugresistance...


Assuntos
Humanos , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral , Mutação , Variação Genética
5.
Braz. j. med. biol. res ; 48(9): 777-781, Sept. 2015. ilus
Artigo em Inglês | LILACS | ID: lil-756404

RESUMO

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Infecções Oportunistas Relacionadas com a AIDS/genética , Antivirais/uso terapêutico , Retinite por Citomegalovirus/genética , Farmacorresistência Viral/genética , Ganciclovir/uso terapêutico , Mutação , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Retinite por Citomegalovirus/tratamento farmacológico , Progressão da Doença , DNA Viral/genética , Falha de Tratamento , Carga Viral/efeitos dos fármacos
6.
Braz. j. infect. dis ; 19(3): 291-295, May-Jun/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-751886

RESUMO

Background: Research has shown that hepatitis B virus (HBV) genotypes are closely linked to the clinical manifestations, treatment, and prognosis of the disease. Objective: To study the association between genotype and drug-resistant HBV mutations in 620 Chinese patients with chronic HBV infection. Methods: HBV DNA levels were determined using real-time quantitative PCR in plasma samples. Microarrays were performed for the simultaneous detection of HBV genotypes (HBV/B, C, and D) and drug-resistance-related hotspot mutations. A portion of the samples analyzed using microarrays was selected randomly and the data were confirmed using direct DNA sequencing. Results: Most samples were genotype C (471/620; 76.0%), followed by genotype B (149/620; 24.0%). Among the 620 patient samples, 17 (2.7%) had nucleotide analogs (NA) resistance-related mutations. Of these, nine and eight patients carried lamivudine (LAM)-/telbivudine (LdT)-resistance mutations (rtL180M, rtM204I/V) and adefovir (ADV)-resistance mutations (rtA181T/V, rtN236T), respectively. No patients had both lamivudine (LAM)- and either ade-fovir (ADV) or entecavir (ETV) resistance mutations. Additionally, out of the 620 patient samples, 64.0% (397/620) were also detected with the precore stop-codon mutation (G1896A) by microarray assay. Conclusion: The results of the current study revealed that the prevalence of nucleotide analogs (NA)-resistance in Chinese hospitalized HBV-positive patients was so low that intensive nucleotide analogs (NA)-resistance testing before nucleotide analog (NA) treatment might not be required. In addition, the present study suggests that chronic HBV patients with genotype C were infected with fitter viruses and had an increased prevalence of nucleotide analogs (NA)-resistance mutations compared to genotype B virus. .


Assuntos
Adulto , Feminino , Humanos , Masculino , Antivirais/administração & dosagem , Farmacorresistência Viral/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Mutação , Grupo com Ancestrais do Continente Asiático , Adenina/administração & dosagem , Adenina/análogos & derivados , DNA Viral/genética , Genótipo , Guanina/administração & dosagem , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , Análise em Microsséries , Organofosfonatos/administração & dosagem , Prognóstico , Análise de Sequência de DNA , Timidina/administração & dosagem , Timidina/análogos & derivados
7.
Medicina (B.Aires) ; 75(3): 163-168, June 2015. tab
Artigo em Espanhol | LILACS | ID: lil-757098

RESUMO

La vigilancia de resistencia primaria de HIV es fundamental para optimizar el tratamiento antirretroviral (TARV) de la infección. Las mutaciones a vigilar están definidas en una lista de referencia de la Organización Mundial de la Salud (OMS), que no incluye mutaciones para drogas nuevas como la rilpivirina. Revisamos retrospectivamente las historias clínicas de pacientes naive de TARV asistidos en 2011-2013 en un centro privado de derivación de HIV/Sida, pesquisando mutaciones según criterios de OMS y mutaciones específicas de resistencia a rilpivirina. Incluimos 91 pacientes; 71 (78.0%) eran hombres y 46 (50.5%) eran hombres que tenían sexo con hombres; 34 (37.4%) presentaban infección temprana y 60 (65.9%) estaban asintomáticos. Los valores medianos de edad, carga viral y recuento de CD4 fueron 33 años, 62 100 copias/ml y 548 células/μl, respectivamente. Encontramos mutaciones de lista OMS en 11 (12.1%) pacientes, dos de ellos presentaron mutaciones a dos familias de drogas. Siete mutaciones correspondieron a inhibidores no nucleosídicos de la retrotranscriptasa, cuatro a análogos nucleosídicos y dos a inhibidores de la proteasa; las más frecuentes fueron K103N y M41L. No hubo mayor frecuencia de mutaciones en pacientes con infección temprana, ni diferencias según sexo, orientación sexual o recuento de CD4. Tres pacientes (3.3%) presentaron mutaciones asociadas a bajos niveles de resistencia a rilpivirina (E138A, E138G). Los niveles de resistencia primaria observados en este estudio evidencian la importancia de determinar resistencia previo al inicio de TARV en la población asistida en nuestro centro. La prevalencia observada de resistencia primaria a rilpivirina fue baja.


Surveillance of primary drug resistance is critical to optimize antiretroviral therapy (ART) for HIV. Mutations to be monitored are defined in a reference list of the World Health Organization (WHO), which does not include mutations for new drugs, such as rilpivirine. We undertook a retrospective analysis of medical records of ART naive patients treated at a specialized HIV/AIDS center, evaluating the prevalence of WHO mutations and mutations specific for rilpivirine. Ninety-one patients were included during 2011-2013, being male 71 (78.0%), and men who have sex with men 46 (50.5%). The median values for age, viral load, and CD4 counts were 33 years, 62 100 copies/mL, and 548 cells/l, retrospectively; 34 (37.3%) had early infection and 60 (65.9%) were asymptomatic. WHO mutations were found in 11 (12.1%) patients, two of whom presented multiple mutations. Seven mutations corresponded to non-nucleoside reverse transcriptase inhibitors, four to nucleoside analogues, and two to protease inhibitors. The most frequent mutations were K103N and M41L. No differences in mutation frequencies were found when compared by time post-infection, gender, sexual orientation, or CD4 count. Mutations conferring low-level resistance to rilpivirine were found in 3 (3.3%) patients; such mutations were E138A and E138G. The overall moderate primary resistance levels found in this study highlight the value of performing a resistance test before ART initiation in the served population. The observed prevalence of primary resistance to rilpivirine was low.


Assuntos
Adulto , Feminino , Humanos , Masculino , Fármacos Anti-HIV , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1 , Mutação , HIV-1 , Prevalência , Estudos Retrospectivos , População Urbana , Carga Viral
8.
Cad. saúde pública ; 31(4): 701-708, 04/2015. tab, graf
Artigo em Português | LILACS | ID: lil-744862

RESUMO

Este estudo teve como objetivo analisar a validade fatorial confirmatória e a fidedignidade de uma escala de medida da autoeficácia para atividade física em idosos. Participaram 118 idosos (78% mulheres), com idade entre 60 a 90 anos. Para avaliar a análise fatorial confirmatória utilizou-se o programa Mplus 6.1. A fidedignidade foi testada pela consistência interna e estabilidade temporal. A escala original foi composta por cinco itens com resposta dicotômica (não/sim), de maneira independente para caminhada e atividade física moderada e vigorosa. O item relacionado à confiança em realizar atividade física quando o mesmo está de férias foi excluído. Foram identificados dois construtos denominados "autoeficácia para caminhada" e "autoeficácia para atividade física moderada e vigorosa", com carga fatorial ≥ 0,50. Houve adequados valores de consistência interna, tanto para caminhada (> 0,70) quanto para atividade física moderada e vigorosa (> 0,80) e de estabilidade temporal para todos os itens. Conclui-se que a escala de autoeficácia para atividade física apresenta validade, consistência interna e fidedignidade adequada para avaliar esse construto em idosos brasileiros.


This study aimed to analyze the confirmatory factor validity and reliability of a self-efficacy scale for physical activity in a sample of 118 elderly (78% women) from 60 to 90 years of age. Mplus 6.1 was used to evaluate the confirmatory factor analysis. Reliability was tested by internal consistency and temporal stability. The original scale consisted of five items with dichotomous answers (yes/no), independently for walking and moderate and vigorous physical activity. The analysis excluded the item related to confidence in performing physical activities when on vacation. Two constructs were identified, called "self-efficacy for walking" and "self-efficacy for moderate and vigorous physical activity", with a factor load ≥ 0.50. Internal consistency was adequate both for walking (> 0.70) and moderate and vigorous physical activity (> 0.80), and temporal stability was adequate for all the items. In conclusion, the self-efficacy scale for physical activity showed adequate validity, reliability, and internal consistency for evaluating this construct in elderly Brazilians.


El presente estudio tuvo como objetivo analizar la validez del análisis factorial confirmatorio y la confianza en la escala de medida de autoeficacia en la actividad física de ancianos. Participaron 118 ancianos (78% mujeres), cuya edad fue de 60 a 90 años. Para evaluar el análisis factorial confirmatorio se utilizó el programa Mplus 6.1. La confianza fue comprobada por la consistencia interna y la estabilidad temporal. La escala original estaba compuesta por cinco ítems con respuesta dicotómica (no/sí), de manera independiente para la actividad física moderada y vigorosa. El ítem relacionado con la confianza para realizar la actividad física cuando el sujeto está de vacaciones fue excluido. Fueron identificados dos constructos denominados "autoeficacia para caminata" y "autoeficacia para actividad física moderada y vigorosa", con carga factorial ≥ 0,50. Hubo adecuados valores de consistencia interna, tanto para la caminata (> 0,70), como para la actividad física moderada y vigorosa (> 0,80), y de estabilidad temporal para todos los ítems. Se concluye que la escala de autoeficacia para actividad física presenta validez, consistencia interna y confianza adecuada para evaluar ese constructo en ancianos brasileños.


Assuntos
Humanos , Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1 , África/epidemiologia , Fármacos Anti-HIV/economia , Análise Custo-Benefício , Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1 , Organização Mundial da Saúde
10.
J Antimicrob Chemother ; 70(3): 926-929, 2015.
Artigo em Inglês | LILACS, Sec. Est. Saúde SP, SESSP-IALPROD, Sec. Est. Saúde SP, SESSP-IALACERVO | ID: biblio-1022184

RESUMO

OBJECTIVES: Dolutegravir is a second-generation integrase strand transfer inhibitor (InSTI) that has been recently approved by the FDA to treat antiretroviral therapy-naive as well as treatment-experienced HIV-infected individuals, including those already exposed to the first-generation InSTI. Despite having a different mutational profile, some cross-resistance mutations may influence its susceptibility. The aim of this study was to evaluate the impact of a raltegravir-containing salvage regimen on dolutegravir activity. PATIENTS AND METHODS: Blood samples of 92 HIV-infected individuals with virological failure (two or more viral loads >50 copies/mL after 6 months of treatment) using raltegravir with optimized background therapy were sequenced and evaluated according to the Stanford University HIV Drug Resistance Database algorithm. RESULTS: Among the 92 patients analysed, 32 (35%) showed resistance to dolutegravir, in most cases associated with the combination of Q148H/R/K with G140S/A mutations. At genotyping, patients with resistance to dolutegravir had viral load values closer to the highest previously documented viral load. CONCLUSIONS: Changes in viraemia during virological failure may indicate the evolution of raltegravir resistance and may predict the emergence of secondary mutations that are associated with a decrease in dolutegravir susceptibility. Early discontinuation of raltegravir from failing regimens might favour subsequent salvage with dolutegravir, but further studies are necessary to evaluate this issue.


Assuntos
Pirrolidinonas/uso terapêutico , Humanos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Terapia de Salvação/métodos , Falha de Tratamento , Análise de Sequência de DNA , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Adulto , Mutação de Sentido Incorreto , Farmacorresistência Viral , Adulto Jovem , Raltegravir Potássico , Genótipo , Compostos Heterocíclicos/farmacologia , Pessoa de Meia-Idade
11.
São Paulo; s.n; 2015. [115] p. tab, graf.
Tese em Português | LILACS, Sec. Est. Saúde SP, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-ACVSES, SESSP-TESESESSP, Sec. Est. Saúde SP | ID: biblio-1083389

RESUMO

Crianças e adolescentes em uso de terapia antirretroviral de alta atividade(HAART) caracterizam um grupo especialmente vulnerável no contexto daepidemia pelo HIV-1...O presente estudo tem como objetivo avaliar os genes da protease e transcriptase reversa em crianças e adolescentes vivendo comHIV/aids. Foi realizada uma análise retrospectiva... Entre os pacientes expostos às três classes com mais de uma entrada (n=27), não houve aumento de mutação para essas classes em relação a genotipagemimediatamente anterior. A alta proporção de resistência aos IP em subtipos Fobservada nesse estudo sugere que o uso dos IP deve ser avaliado levandoem consideração o possível impacto na resposta terapêutica. Os dadosdesse estudo demonstram uma taxa intermediária de resistência transmitidae uma elevada proporção de casos com resistência entre os pacientes emfalha, embasa a noção de que esta população representa um segmento derisco para a evolução da doença.


Children and adolescents on highly active antiretroviral therapy (HAART)represents a vulnerable group in the context of the HIV-1 epidemic, due tobiological issues and different socio-behavioral aspects such as those relatedto adherence to HAART... A retrospective analysis was made, in samples collected from naïve patients and patients exposed to antiretrovirals(ART) with virological failure...Among patients exposed to the three ART classes with more than one genotyping test (n=27), mutations prevalence seemed to not increase when we compared with the previous genotyping test, however most of patients samples showed resistance to the main ART available for use. The high proportion of resistance to IP among subtype F suggests thatin these cases, the IP administration should be evaluated considering apossible impact on therapeutic response. Our results showed an intermediaterate of transmitted resistance e a high proportion of resistance amongpatients with virological failure, supporting the fact that this populationrepresents more risk to disease progression.


Assuntos
Humanos , Criança , Adolescente , HIV-1 , Adolescente , Criança , Farmacorresistência Viral/genética , Mutação , Terapia Antirretroviral de Alta Atividade/tendências
12.
Cienc. tecnol. salud ; 1(1): 5-12, jul.-dic. 2014. ilus, graf
Artigo em Espanhol | LILACS | ID: biblio-834305

RESUMO

La resistencia a la terapia antirretroviral (TARV) es un factor determinante para el fallo virológico en pacientes con VIH. El objetivo de este estudio fue identificar los patrones genotípicos de resistencia en pacientes con fallo virológico. Fueron incluidos pacientes de las diferentes unidades de atención integral de VIH en Guatemala, de quienes se sospechaba resistencia y que necesitaban cambios en la TARV por fallo virológico, se requirió haber evaluado la adherencia y una carga viral ≥1,000 copias/ml. La información clínica y demográfica fue recolectada a través de la forma de solicitud. El análisis de resistencia se realizó a través de la metodología TRUGENE® HIV-1. La muestra se restringió a 25 pacientes por motivos de accesibilidad. El 68% de las muestras analizadas presentaron resistencia; por familia de ARV la resistencia fue de 88.2% para ITINN, 70.5% para ITIAN y 17.6% para IP. Se identificaron 79 mutaciones entre el grupo de estudio, el 46.8% de fueron asociadas a ITINN, 76.6% a ITIAN y 26.6% a IP. Para ITIAN las mutaciones más frecuentes fueron la M184V 43%, M184I 14% y K219E 10%; el 23.8% fueron mutaciones TAMs. Para ITINN fueron la V179D 16%, K103N 14%, G190A 14% y Y181C 14%. Para los IP la mutación más frecuente fue la M36I con 29%. La resistencia identificada en este grupo, fue menor a lo reportado en otros países latinoamericanos; sin embargo es similar a lo reportado por OMS en países con bajo o medio ingreso económico.


ARV drug resistance is one of the leading causes of virologic failure among HIV patients on HAART. Theobjective of this study was to determine genotypic resistance profiles among HIV patients on virologic failure. Patients from one HIV clinic in Guatemala on whom ARV drug resistance was suspected and needed a change in their ARV regimen due to virologic failure were included. In order to perform the genotype, the patient had to demonstrate good adherence to therapy and a confirmed viral load ≥1,000 copies/ml. Demographics andclinical data were collected through the resistance-testing questionnaire. The TRUGENE® HIV-1 methodology was used for resistance analysis. The patient sample was restricted to 25 patients due to accessibility, 68% presented resistance to at least one ARV drug. By ARV class, 88.2% presented resistance to NNRTIs, 70.5% to NRTIs and 17.6% to IPs. We found 79 mutations among the samples analyzed. Of the mutations found, 46.8% were associated with NNRTI resistance, 76.6% to NRTI resistance and the remainder 26.6% to PI resistance. The most frequent NRTI associated mutations were M184V 43%, M184I 14% and K219E 10%; 23.8% were TAM. The NNRTI associated mutations were V179D 16%, K103N 14%, G190A 14% and Y181C 14%. For the PI the most frequent mutation was M36I with 29%. The resistance found in this study was lower to that reported in other Latin American studies, however, it is similar to what is reported by WHO in low and middle income countries.


Assuntos
Humanos , Masculino , Feminino , Farmacorresistência Viral , HIV-1 , Antirretrovirais/imunologia , Mutação
13.
Rev. cuba. med ; 53(4): 445-455, sep.-dic. 2014.
Artigo em Espanhol | LILACS, CUMED | ID: lil-735342

RESUMO

INTRODUCCIÓN: la emergencia de virus de inmunodeficiencia humana tipo 1 (VIH-1) resistentes a antirretrovirales constituye una de las principales causas de fallo terapéutico. OBJETIVO: analizar las mutaciones asociadas a resistencia a los antirretrovirales y los niveles de resistencia en un grupo de pacientes con criterios de fallo a la terapia antirretroviral de gran actividad (TARGA) durante el año 2012.MÉTODOS: se colectaron muestras de plasma de 25 individuos con criterios de fallo a la TARGA, de los 157 pacientes positivos al VIH-1 que asistieron a la Consulta Externa de Infectología del Hospital "Hermanos Ameijeiras" durante el año 2012. Se determinó el subtipo viral y las mutaciones asociadas a resistencia y se estimó el tiempo transcurrido entre el inicio de la última terapia y la detección de virus resistente. RESULTADOS: 52 % de los pacientes solamente había recibido un régimen de TARGA. Se detectaron mutaciones asociadas a resistencia en 84 % de los pacientes. El 64 % presentó alta resistencia a los antirretrovirales empleados como primera estrategia terapéutica en el país. El tiempo promedio entre el inicio de la última terapia y la detección de virus resistente fue de 2,3 años. El 16 % de los pacientes presentó virus susceptibles, en este grupo la probabilidad de no adherencia a la TARGA pudo ser la causa del fallo terapéutico. CONCLUSIONES: se evidenciaron altos niveles de resistencia a la primera línea de TARGA empleada en Cuba y la aparición de variantes resistentes después de iniciar el tratamiento. Estos resultados enfatizan la necesidad del monitoreo de la resistencia como parte de la atención integral a las personas que viven con VIH/Sida.


INTRODUCTION: the emergence of resistant virus antiretroviral human immunodeficiency type 1 (HIV-1) is a major cause of treatment failure. OBJECTIVE: to analyze the mutations associated with antiretroviral resistance and resistance levels in a group of patients with failure criteria to antiretroviral therapy (HAART). METHODS: Plasma samples from 25 individuals with failure criteria to HAART were collected out of 157 HIV-1 positive patients attending the Outpatient Infectious Diseases at Hermanos Ameijeiras Hospital during 2012. The viral subtype and resistance mutations were determined; and the time between the beginning of the last therapy and detection of resistant viruses was estimated time. RESULTS: 52 % of patients had only received HAART regimen. Mutations associated with resistance in 84 % of patients were detected. 64 % had to antiretroviral treatment strategy employed as first high resistance in this country. The average time between the beginning of the last therapy and the detection of resistant viruses was 2.3 years. 16 % of patients had susceptible virus. The probability of non-adherence to HAART could be the cause of therapeutic failure in this group. CONCLUSIONS: high levels of resistance to first-line HAART used in Cuba and the emergence of resistant variants after starting treatment were evident. These results emphasize the need for monitoring resistance as part of comprehensive care for people living with HIV / AIDS.


Assuntos
Humanos , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Antirretrovirais/uso terapêutico , Cuba
14.
Mem. Inst. Oswaldo Cruz ; 109(7): 912-917, 11/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-728806

RESUMO

After the World Health Organization officially declared the end of the first pandemic of the XXI century in August 2010, the influenza A(H1N1)pdm09 virus has been disseminated in the human population. In spite of its sustained circulation, very little on phylogenetic data or oseltamivir (OST) resistance is available for the virus in equatorial regions of South America. In order to shed more light on this topic, we analysed the haemagglutinin (HA) and neuraminidase (NA) genes of influenza A(H1N1)pdm09 positive samples collected during the pandemic period in the Pernambuco (PE), a northeastern Brazilian state. Complete HA sequences were compared and amino acid changes were related to clinical outcome. In addition, the H275Y substitution in NA, associated with OST resistance, was investigated by pyrosequencing. Samples from PE were grouped in phylogenetic clades 6 and 7, being clustered together with sequences from South and Southeast Brazil. The D222N/G HA gene mutation, associated with severity, was found in one deceased patient that was pregnant. Additionally, the HA mutation K308E, which appeared in Brazil in 2010 and was only detected worldwide the following year, was identified in samples from hospitalised cases. The resistance marker H275Y was not identified in samples tested. However, broader studies are needed to establish the real frequency of resistance in this Brazilian region.


Assuntos
Feminino , Humanos , Gravidez , Hemaglutininas/genética , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Neuraminidase/genética , Pandemias , Antivirais/uso terapêutico , Biomarcadores/análise , Brasil/epidemiologia , Farmacorresistência Viral/fisiologia , Frequência do Gene/genética , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/virologia , Mutação/genética , Oseltamivir/uso terapêutico , Filogenia , RNA Viral/análise , Análise de Sequência de DNA/métodos , Virulência , Fatores de Virulência/genética
15.
Actual. SIDA. infectol ; 22(85): 47-52, set.2014. ilus
Artigo em Espanhol | LILACS | ID: lil-780404

RESUMO

Dolutegravir (DTG) es un inhibidor de la integrasa del VIH aprobado recientemente como tratamiento por la FDA (Food and Drug Administration) en los Estados Unidos. Utilizado como parte de un tratamiento de primera línea, DTG es el único tratamiento antirretroviral frente al cual no se ha seleccionado resistencia en la clínica. Nuestra teoría es que esto se debe al prolongado tiempo de unión del DTG a la enzima integrasa así como a una capacidad de replicación muy disminuida por parte de los virus que podrían volverse resistentes al DTG. Además, conjeturamos que DTG podría ser utilizado en estrategias que apunten a la erradicación del VIH...


Dolutegravir (DTG) is an HIV integrase inhibitor that was recently approved for therapy by the Food and Drug Administration in the United States. When used as part of First-line therapy, DTG is the only HIV drug that has not selected for resistance mutations in the clinic. We believe that this is due to the long binding time of DTG to the integrase enzyme as well as greatly diminished replication capacity on the parte of viruses that might become resistant to DTG. We further speculatethat DTG might be able to be used in strategies aimed at HIV eradication...


Assuntos
Humanos , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral , Inibidores da Protease de HIV/farmacologia , Integrase de HIV/uso terapêutico , Mutação
16.
Rev. cuba. med ; 53(2): 127-133, abr.-jun. 2014.
Artigo em Espanhol | LILACS | ID: lil-722965

RESUMO

Introducción: el empleo de la terapia antirretroviral ha facilitado la recuperación lenta y parcial del sistema inmune, lo que permite reducir las complicaciones oportunistas, incrementar la supervivencia y mejorar la calidad de vida en pacientes infectados por el virus de inmunodeficiencia humana tipo 1. Objetivo: determinar las variantes virales de evolución rápida a la resistencia a drogas antirretrovirales en pacientes positivos a VIH-1. Métodos: se estudiaron 2 pacientes positivos a VIH-1; se nombraron con las letras A y B, respectivamente, y se les determinó la resistencia a drogas antirretrovirales en 2 tiempos diferentes: momento del diagnóstico y 2012. Los resultados se relacionaron con variables clínicas. Resultados: el paciente A, en el momento del diagnóstico, presentó un virus subtipo BG con niveles bajos de resistencia a zidovudina y estavudina y el B, virus subtipo B, con bajos niveles de resistencia a zidovudina. En el año 2012, el paciente A mostró una variante viral FRC18_cpx con altos niveles de resistencia a lamivudina, emtricitabina y nevirapina. El paciente B se mantuvo infectado con un virus subtipo B, pero resistente a los inhibidores de la transcriptasa inversa. Conclusiones: estos resultados muestran la dinámica y rápida evolución de las variantes de VIH-1 en pacientes infectados...


Introduction: the use of antiretroviral therapy has facilitated the slow and partial recovery of the immune system, allowing to reduce opportunistic complications, to increase survival and to improve quality of life in patients infected with human immunodeficiency virus type 1. Objective: to determine rapid evolving viral variants with resistance to antiretroviral drugs in HIV-1 positive patients. Methods: two HIV-1 positive patients were studied. They were appointed by the letters A and B, respectively, and antiretroviral drug resistance were determined at two different times: Moment of diagnosis and 2012. Results were related to clinical variables. Results: at the time of diagnosis Patient A had subtype BG virus with low levels of resistance to zidovudine and stavudine. Patient B had subtype B virus with low levels of resistance to zidovudine. In 2012, the patient A showed FRC18-cpx viral variant with high levels of resistance to lamivudine, emtricitabine, and nevirapine. Patient B remained infected with subtype B virus, but resistant to the reverse transcriptase inhibitors. Conclusions: these results show the dynamic and rapidly evolving variants of HIV-1 infected patients...


Assuntos
Humanos , Antirretrovirais/uso terapêutico , Farmacorresistência Viral , HIV-1 , Estudos de Casos e Controles
17.
Braz. j. infect. dis ; 18(1): 1-7, Jan-Feb/2014. tab
Artigo em Inglês | LILACS | ID: lil-703060

RESUMO

Background: Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil. Methods: Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load <50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression. Results: Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI = 69.7–86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI = 103.4–159.6). In multiple logistic regression analysis, higher baseline viral load (RR = 1.04 per 10,000 copies/mL increase; 95% CI = 1.01–1.09) and higher number of darunavir resistance-associated mutations (RR = 1.23 per each; 95% CI = 0.95–1.48) ...


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Terapia de Salvação , Sulfonamidas/uso terapêutico , Brasil , Farmacorresistência Viral/genética , Genótipo , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1 , Estudos Retrospectivos , Carga Viral
18.
Rev. panam. infectol ; 16(1): 57-61, 2014.
Artigo em Português | LILACS, Sec. Est. Saúde SP | ID: biblio-1067139

RESUMO

A resistência viral aos inibidores de protease aparece rapidamente, pois essas cepas resistentes já existem naturalmente na população de quasispécies do vírus, emergindo como cepas mais prevalentes em relação às cepas selvagens quando o vírus sofre a pressão da droga. Esta seleção de cepas resistentes (RAVs) tem um papel im¬portante na falha terapêutica dessa classe de droga. Análise por sequenciamento direto em pacientes não tratados têm demonstrado diversas RAVs aos inibidores de protease (substituições nas posi¬ções V36, T54, V55, Q80, R155, D168 e V170). As mutações nas posições R155K e A156T da região NS3 estão associadas à alta resistência aos inibidores de protease. Dessa forma, os antivirais de ação direta (DAA) não podem ser utilizados em monoterapia. Aparentemente, existe uma diferença geográfica na distribuição dessas variantes de resistência. Nas populações europeia e america¬na, por exemplo, a variante de resistência na posição Q80K no ge¬nótipo 1a, que confere resistência ao simeprevir, foi encontrada em 25% a 35%. No entanto, na população brasileira uma frequência em torno de 1,8% de RAVs na posição Q80K, em três estudos, dois em VHC monoinfectados e outro em co-infectados VHC-HIV. O conhecimento da distribuição dos subgenótipos e do perfil de mutações nas diversas populações em todo o mundo vai se tornar importante na confecção de guidelines regionais, que seguramente terão suas particularidades de acordo com o perfil de cada região, no intuito de atingirmos máxima eficácia dos diferentes esquemas terapêuticos


Viral resistance to protease inhibitors appear quickly because these resistant strains occur naturally in the virus quasispecies population, emerging as the most prevalent strains compared to wild type strains when the virus is under drug pressure. This selection of resistant strains (RAVs) has an important role in therapeutic failure of this class of drug. Analyses by direct sequencing in untreated patients have shown various RAVs to protease inhibitors (substitutions at positions V36, T54, V55, Q80, R155, A156, D168 and V170). Mutations at positions R155K and A156T on NS3 region are associated with high resistance to protease inhibitors. Thus, the direct action antivirals (DAA) may not be used as monotherapy. Apparently, there is a geographical difference in the distribution of these variants of resistance worldwide. In European and American HCV population for example, resistance variants in the position Q80K genotype 1a, which confers resistance to simeprevir was found in 25% to 35% of patients. However, in the Brazilian population the Q80K mutation was found at a frequency of around 1.8%, in three studies, two in HCV monoinfected and another in coinfected HIV-HCV patients. The distribution of this mutation profile in different populations around the world will become important in the preparation of regional guidelines, which surely will have their particularities according to the HCV subtyping distribution and mutation profile of each region in order to achieve maximum effectiveness of different treatment regimens


Assuntos
Hepacivirus , Hepatite C , Hepatite C Crônica , Farmacorresistência Viral , Genótipo , Inibidores de Proteases
19.
Biomédica (Bogotá) ; 33(4): 631-642, Dec. 2013. graf, tab
Artigo em Espanhol | LILACS | ID: lil-700480

RESUMO

Introducción. En Colombia se ha publicado poco sobre farmacorresistencia del VIH en pacientes que reciben tratamiento antirretroviral. Las guías de VIH de Colombia de 2006, no recomiendan el uso de los estudios de genotipo de resistencia en pacientes nunca expuestos a medicamentos antirretrovirales ni después del primer fracaso terapéutico. Objetivo. Determinar la frecuencia de mutaciones de resistencia y el grado de sensibilidad/resistencia del VIH a los antirretrovirales en pacientes que han recibido tratamiento antirretroviral. Materiales y métodos. Se reclutó una muestra no probabilística de 170 pacientes con infección por VIH que recibían tratamiento antirretroviral, experimentaban fracaso virológico y que tenían estudios de genotipo de resistencia. Se estudió la farmacorresistencia del VIH en dos grupos: estudios de genotipo de resistencia tempranos Vs . tardíos. Resultados. El tipo de resistencia más frecuente en pacientes bajo tratamiento antirretroviral, afectó a los inhibidores no nucleosídicos (76 %). El grupo de estudio tardío tuvo mayor riesgo de resistencia a inhibidores nucleosídicos y a los inhibidores de proteasa, mayor número de mutaciones de resistencia y mayor complejidad de las resistencias, que el grupo de estudio temprano. También, se encontró un alto grado (30 %) de resistencia cruzada a los inhibidores nucleosídicos en el grupo de estudio tardío. Los medicamentos menos afectados fueron tenofovir y darunavir. Conclusiones. Los resultados de este estudio sugieren que practicar estudios de genotipo de resistencia tardíos se asocia con altos niveles de resistencia, lo cual puede restringir el uso de un gran número de antirretrovirales esenciales en esquemas subsiguientes. Es necesario revisar las actuales recomendaciones sobre el uso de dichos exámenes en las guías colombianas de manejo de VIH.


Introduction: Little has been published in Colombia on HIV drug resistance in patients taking antiretroviral treatment (ART). Currently, the Colombian guidelines do not recommend the use of genotypic antiretroviral resistance tests (GART) for treatment-naive patients or for those experiencing a first therapeutic failure. Objective: To determine the frequency of relevant resistance mutations and the degree of susceptibility/ resistance of HIV to antiretroviral drugs (ARVs) in ART-experienced patients. Materials and methods: A non-random sample of 170 ART-experienced HIV patients with virologic failure and who underwent GART was recruited. A study of HIV drug resistance was carried out in two groups of patients: one group that underwent early GART and the other group that received late GART testing. Results: The most frequent type of resistance affected the non-nucleoside class (76%). The late-GART group had higher risk of nucleoside analog and protease inhibitor drug resistance, a higher number of resistance mutations and more complex mutational profiles than the early-GART group. A high cross resistance level (30%) was found in the nucleoside analog class. The least affected medications were tenofovir and darunavir. Conclusions: Our results suggest that performing GART late is associated with levels of ARV resistance that could restrict the use of an important number of essential ARV in subsequent regimens. There is a need to revise the current recommendations to include GART prior to start of treatment and after the first virologic failure.


Assuntos
Adulto , Feminino , Humanos , Masculino , Antirretrovirais/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Antirretrovirais/farmacologia , Colômbia , Estudos Transversais , HIV-1 , Mutação , Fatores de Tempo
20.
Rev. chil. infectol ; 30(6): 630-637, dic. 2013. ilus
Artigo em Espanhol | LILACS | ID: lil-701712

RESUMO

Objective: To assess the secondary resistance patterns of HIV-1to Anti-Retroviral Agents drugs (ART) in patients with virological failure in the main HIV care center in Guatemala. Methods: Using the Stanford HIV Database,HIV pol sequences were analyzed to obtain resistance patterns in patients with first-failure to ART or multiple-failures (2 or more regimens failed), from 2008 to 2012. Proportions and odds ratio (OR) with 95% confidence intervals (95%CI) were calculated. Results: 83% (43) in the first-failure and 75% (30) in multiple-failures had resistance. The highest frequency (70%)of resistance was found in the non-nucleoside-inhibitors ART family. 44% (42) showed resistance to two ART families and 4% (4) to the three families. First-failure patients had higher risk of nucleoside-inhibitor resistance (OR:3.0, 95%CI 1.29-6.98) and multidrug resistance (OR:4.94, 95%CI 1.98-12.32). Most frequent mutations were: M184V, K103N and K65R (71, 50 and 22%, respectively). 70% of patients with first-failure were resistant to at least one of the drugs used as second ART in Guatemala (ABC, ddI or AZT). Conclusions: The high level of HIV-1 resistance to ART observed, suggest the need to amend the current second line regimen treatments in Guatemala and the importance of viral genotyping in all patients with first-failure to ART.


Objetivo: Evaluar el perfil de resistencia secundaria del VIH-1 a anti-retrovirales (ARV) en pacientes con fallo virológico en la clínica de atención integral más grande de Guatemala. Métodos: Uso de Stanford HIV Database para análisis de secuencias pol para perfiles de resistencia de VIH en pacientes con fallo virológico al primer esquema ARV o fallo múltiple (dos o más esquemas ARV fallidos), entre los años 2008 y 2012. Determinación de proporciones y análisis de riesgo. Resultados: Evidencia de resistencia de 83% (n: 43) en primer fallo y 75% (n: 30) en fallo múltiple. La mayor frecuencia de resistencia se presentó en los inhibidores-no-nucleosídicos (70%). Cuarenta y cuatro por ciento (n: 42) evidenció resistencia a dos familias de ARV y 4% (n: 4) a las tres familias. Pacientes con primer fallo tuvieron más riesgo de resistencia a inhibidores-nucleosídicos (OR: 3,0; IC 95% 1,29-6,98) y más riesgo de multi-resistencia (OR: 4,94; IC 95% 1,98-12,32). Mutaciones más frecuentes fueron: M184V, K103N y K65R (71, 50 y 22%, respectivamente). Setenta por ciento de los pacientes con primer fallo presentaron resistencia a al menos uno de los medicamentos utilizado como segunda línea en Guatemala (ABC/ddI/AZT). Conclusiones: El alto nivel de resistencia del VIH-1 a los ARV observada, sugiere la necesidad de modificar el actual esquema terapéutico de rescate en Guatemala y la importancia de realizar genotipificación viral en todos los pacientes con fallo al primer esquema.


Assuntos
Adulto , Feminino , Humanos , Masculino , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1 , Mutação/genética , Genótipo , Guatemala , Infecções por HIV/tratamento farmacológico , HIV-1 , Estudos Retrospectivos , Falha de Tratamento , Carga Viral
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