ABSTRACT
La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.
Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , HIV Infections/drug therapy , HIV-1/genetics , HIV Integrase Inhibitors/therapeutic use , HIV Integrase Inhibitors/pharmacology , Anti-HIV Agents/therapeutic use , Uruguay , Raltegravir Potassium/therapeutic use , Raltegravir Potassium/pharmacology , MutationABSTRACT
RESUMO A terapia antirretroviral interfere na replicação do vírus HIV, impede a progressão da infecção para a Aids e previne a mortalidade precoce das crianças infectadas. Esta pesquisa investigou o perfil sociodemográfico e os parâmetros relacionados com o tratamento antirretroviral das crianças HIV positivas residentes no estado do Paraná. Trata-se de um estudo observacional descritivo e analítico realizado com dados secundários do ano de 2020 referentes às crianças com até 12 anos de idade. Foram investigados: perfil, prevalência, medicamentos em uso, abandono da terapia, resistência e supressão viral. Foram identificadas 148 crianças, com uma prevalência igual a 8,1/100 mil no Paraná. Apesar de todas as crianças diagnosticadas com HIV terem iniciado o tratamento, 17,2% encontravam-se em abandono da terapia antirretroviral. Entre as crianças que permaneciam em tratamento, 9,8% não atingiram a supressão viral e suas cargas virais comumente ultrapassavam mil cópias virais/mL. Houve um predomínio de esquemas medicamentosos provavelmente prescritos após falhas terapêuticas. Os resultados indicam que o Paraná apresenta bons resultados quanto ao início rápido da terapia e à supressão viral das crianças. Entretanto, existe um número considerável de abandonos da terapia e de falhas terapêuticas, indicando a necessidade de reforçar a vinculação desta população aos serviços de saúde.
ABSTRACT Antiretroviral therapy interferes with the replication of the HIV virus, stops the progression of infection, and prevents early mortality in infected children. This research investigated the sociodemographic profile and parameters related to the antiretroviral treatment of HIV positive children living in the state of Paraná. This is a descriptive observational and analytical study, carried out with secondary data from the year 2020, referring to children up to 12 years of age. The profile, prevalence, medicines in use, treatment abandonment, viral resistance, and viral suppression were investigated. A total of 148 children were identified, with a prevalence equal to 8.1/100,000 in Paraná. All infants had begun their treatment, but 17,2% abandoned it. Among children who remained on treatment, 9.8% did not achieve viral suppression and their viral loads commonly exceeded 1000 viral copies/mL. There was a predominance of drug regimens probably prescribed after treatment failures. The results indicate that Paraná presents good results in terms of rapid initiation of therapy and viral suppression in children. However, there is a considerable number of abandonments of therapy and therapeutic failures, indicating the need to strengthen the link between this population and health services.
ABSTRACT
El SARS-CoV-2, agente causal de la actual pandemia de la COVID-19, va sufriendo mutaciones como consecuencia de su ciclo evolutivo, lo que ha originado diferentes variantes genéticas, que han sido agrupadas en dos categorías: preocupante (alfa o británica, beta o sudafricana, gamma o brasileña y delta o india) y de interés (lamdba, mu, épsilon, eta, iota, kappa, zeta, theta); estas conllevan implicaciones clínicas en la transmisibilidad, virulencia y resistencia del SARS-CoV-2 a la inmunidad natural y adquirida, lo que representa un serio desafío para los servicios de salud en todo el mundo. En este artículo se describen dichas variantes genéticas, con énfasis en su probable impacto clínico, y además se plantea la posibilidad de que aparezcan otras, como fenómeno natural en la evolución de los virus.
The SARS-CoV-2, causal agent of the COVID-19 current pandemic, is suffering mutations as a consequence of its evolutive cycle, what has originated different genetic variants that have been grouped in two categories: worrying (alpha or British, beta or South African, gamma or Brazilian and delta or Indian) and of interest (lamdba, mu, epsilon, eta, iota, kappa, zed, theta); these categories bear clinical implications in the transmissibility, virulence and resistance from SARS-CoV-2 to the natural and acquired immunity, what represents a serious challenge in health services worldwide. These genetic variants are described in this work, with emphasis in its probable clinical impact, and the possibility that other variants could appear is also explained, as natural phenomenon in the evolution of viruses.
Subject(s)
Coronavirus , SARS-CoV-2/genetics , COVID-19 , Drug Resistance, Viral , MutationABSTRACT
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...
Subject(s)
Humans , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , Mutation , Genetic VariationABSTRACT
Objective. To describe the virological characteristics of the influenza strains circulating in Argentina in 20052008 and to assess the prevalence of antiviral resistance. Methods. On the basis of their geographical spread and prevalence, influenza A and B isolates grown in MadinDarby canine kidney cells were selected after antigenic and genomic characterization to be analyzed for antiviral resistance by enzymatic assay and pyrosequencing. Amantadine susceptibility was evaluated by pyrosequencing for known resistance markers on 45 strains of influenza A. Susceptibility to oseltamivir and zanamivir was evaluated by enzymatic assay of 67 influenza A and 46 influenza B strains, some of which were further analyzed by sequencing the neuraminidase gene. Results. Resistance to amantadine was observed only on A(H3N2) strains (29/33); all of them carried the mutation S31N in their M2 sequence. Oseltamivir resistance was observed in 12 (34.3%) of the 35 A(H1N1) strains from 2008; all of them carried the mutation H275Y in their neuraminidase sequence. All these viruses remained sensitive to zanamivir. Conclusions. This study describes a high incidence of amantadine-resistant influenza A(H3N2) viruses since 2006 and an unprecedented increase in oseltamivir resistance detected only in influenza A(H1N1) viruses isolated in 2008. Influenza A and B viruses were more sensitive to oseltamivir than to zanamivir, and influenza A viruses were more sensitive to both neuraminidase inhibitors than the influenza B viruses. The national data generated and analyzed in this study may help increase knowledge about influenza antiviral drug resistance, which is a problem of global concern.
Objetivo. Describir las características virológicas de las cepas de virus de la gripe que circulaban en la Argentina entre el 2005 y el 2008, y evaluar la prevalencia de la resistencia a los antivíricos. Métodos. Según su diseminación geográfica y su prevalencia, se seleccionaron aislados de gripe A y B cultivados en células renales caninas de Madin-Darby después de su caracterización antigénica y genómica, y se analizó su resistencia a los antivíricos mediante análisis enzimático y pirosecuenciación. La sensibilidad a la amantadina se evaluó por pirosecuenciación para los marcadores conocidos de resistencia en 45 cepas de gripe A. La sensibilidad al oseltamivir y al zanamivir se evaluó mediante análisis enzimático de 67 cepas de gripe A y 46 cepas de gripe B, algunas de las cuales se analizaron en mayor profundidad mediante la secuenciación del gen de la neuraminidasa. Resultados. Se observó resistencia a la amantadina solo en las cepas de gripe A (H3N2) (29/33); todas ellas tenían la mutación S31N en su secuencia de M2. Se observó resistencia al oseltamivir en 12 (34,3%) de las 35 cepas de gripe A (H1N1) aisladas en el 2008; todas ellas tenían la mutación H275Y en su secuencia de neuraminidasa. Todos estos virus conservaron su sensibilidad al zanamivir. Conclusiones. En este estudio se describe una incidencia elevada del virus de la gripe A (H3N2) resistente a la amantadina desde el 2006 y un aumento sin precedentes de la resistencia al oseltamivir detectada solo en los virus de la gripe A (H1N1) aislados en el 2008. Los virus de la gripe A y B fueron más sensibles al oseltamivir que al zanamivir y los virus de la gripe A fueron más sensibles a ambos inhibidores de la neuraminidasa que los virus de la gripe B. Los datos nacionales generados y analizados en este estudio pueden ayudar a aumentar los conocimientos acerca de la resistencia a los fármacos antivíricos dirigidos contra el virus de la gripe, lo que es un motivo de preocupación mundial.