HIV Drug-resistant Strains as Epidemiologic Sentinels

The decrease in the proportion of drug resistance among newly infected HIV-1 patients may signal a worsening of the epidemic

Prevalence of Transmitted Drug Resistance and Impact of Transmitted Resistance on Treatment Success in the German HIV-1 Seroconverter Cohort

BACKGROUND: The aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort. METHODS: Genotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008). A genotypic resistance result was obtained for 1,276/1,312 (97.3%). The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml. RESULTS: Prevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N = 158/1,276; 12.4%; CI(wilson) 10.7-14.3; p(for trend) = 0.25). NRTI resistance was predominant (7.5%) but decreased significantly over time (CI(Wilson): 6.2-9.1, p(for trend) = 0.02). NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson): 2.6-4.6; p(for trend)= 0.07), whereas PI resistance remained stable (PI: 3.0%; CI(Wilson): 2.1-4.0; p(for trend) = 0.24). Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%). The majority of NRTI-resistant strains (79.8%) carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61). The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%). CONCLUSION: Overall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected with HIV might be related to the introduction of novel antiretroviral drugs and a wider use of genotypic resistance analysis prior to treatment initiation

Prevalence of Drug-Resistant HIV-1 Variants in Untreated Individuals in Europe: Implications for Clinical Management

BackgroundInfection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis penta increase-spacing 1>MethodsWe determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002 ResultsIn Europe, 1 of 10 antiretroviral-naive patients carried viruses with ⩾1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P=.006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%; P<.01). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from 2.0% (1/49) in 1996-1998 to 8.2% (16/194) in 2000-2001 ConclusionsDrug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are update

Tracing the HIV-1 subtype B mobility in Europe: a phylogeographic approach

<p>Abstract</p> <p>Background</p> <p>The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced.</p> <p>Results</p> <p>In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred.</p> <p>Conclusion</p> <p>Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.</p

The impact of transmission clusters on primary drug resistance in newly diagnosed HIV-1 infection

OBJECTIVES: To monitor HIV-1 transmitted drug resistance (TDR) in a well defined urban area with large access to antiretroviral therapy and to assess the potential source of infection of newly diagnosed HIV individuals. METHODS: All individuals resident in Geneva, Switzerland, with a newly diagnosed HIV infection between 2000 and 2008 were screened for HIV resistance. An infection was considered as recent when the positive test followed a negative screening test within less than 1 year. Phylogenetic analyses were performed by using the maximum likelihood method on pol sequences including 1058 individuals with chronic infection living in Geneva. RESULTS: Of 637 individuals with newly diagnosed HIV infection, 20% had a recent infection. Mutations associated with resistance to at least one drug class were detected in 8.5% [nucleoside reverse transcriptase inhibitors (NRTIs), 6.3%; non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3.5%; protease inhibitors, 1.9%]. TDR (P-trend = 0.015) and, in particular, NNRTI resistance (P = 0.002) increased from 2000 to 2008. Phylogenetic analyses revealed that 34.9% of newly diagnosed individuals, and 52.7% of those with recent infection were linked to transmission clusters. Clusters were more frequent in individuals with TDR than in those with sensitive strains (59.3 vs. 32.6%, respectively; P < 0.0001). Moreover, 84% of newly diagnosed individuals with TDR were part of clusters composed of only newly diagnosed individuals. CONCLUSION: Reconstruction of the HIV transmission networks using phylogenetic analysis shows that newly diagnosed HIV infections are a significant source of onward transmission, particularly of resistant strains, thus suggesting an important self-fueling mechanism for TDR

Herramienta web 2.0, como estrategia pedagógica para el fortalecimiento del nivel crítico intertextual de la comprensión lectora, en los estudiantes de grado quinto de la Institución Educativa Villa de los Andes.

Este proyecto tiene como objeto fortalecer el nivel crítico intertextual de la comprensión lectora mediante la implementación de una herramienta web 2.0 titulada “3,2,1… ¡Vamos a leer y comprender!” en estudiantes de grado quinto de la Institución Educativa Villa de los Andes Sede Principal, en el que se aplicó encuestas, diarios de campo y grupo de discusión a una muestra poblacional de 29 padres de familia y 4 docentes de aula, al igual que 29 estudiantes respectivamente. Lo anterior, conllevo a realizar cuatro etapas, iniciando por la identificación de debilidades y el estado del nivel crítico intertextual de los niños, luego se diseñó una estrategia pedagógica con cuatro (4) secuencias didácticas mediante una herramienta Web. Como resultado, se estableció que las estrategias pedagógicas como ésta constituyen una propuesta novedosa, capaz de la incorporación de elementos esenciales para favorecer el aprendizaje y la metacognición; lo que conlleva a atraer el interés del estudiante por leer e impulsarlo a mejorar su comprensión lectora, mediante un trabajo colaborativo que posibilita el desarrollo integral. A manera de aporte, se destaca la efectividad y uso pedagógico de las TIC en los escenarios formativos que conllevan a transformar la realidad educativa y contribuir en la mejora del desarrollo actitudinal, los conocimientos y su aplicabilidad favoreciendo en el bienestar familiar, social y educativo.MaestríaMagíster en Recursos Digitales Aplicados a la Educació

Enfermedad de Chagas: un diagnóstico olvidado de serias consecuencias

Para el Instituto de Medicina Tropical, desde su fundaci&oacute;n hace 70 a&ntilde;os, la Enfermedad de Chagas (ECh) ha sido motivo de investigaciones pioneras realizadas por F&eacute;lix Pifano y Alberto Maekelt, en el &aacute;rea de la epidemiolog&iacute;a y el diagn&oacute;stico destac&aacute;ndose los aportes en diagn&oacute;stico serol&oacute;gico, la elaboraci&oacute;n de ant&iacute;geno de Trypanosoma cruzi y la evaluaci&oacute;n de la trasmisi&oacute;n en &aacute;reas rurales. En la Secci&oacute;n de Inmunolog&iacute;a (SI) se realizan varias t&eacute;cnicas para el diagn&oacute;stico parasitol&oacute;gico, inmunol&oacute;gico y molecular de la ECh en sus fases aguda y cr&oacute;nica. Suman 244 casos agudos evaluados en la SI desde 2007 cuando se describe la primera microepidemia de trasmisi&oacute;n oral para Venezuela y la m&aacute;s numerosa en Latinoam&eacute;rica. La detecci&oacute;n simultanea de par&aacute;sitos o su ADN en sangre, y de anticuerpos espec&iacute;ficos en toda la poblaci&oacute;n expuesta facilita el diagn&oacute;stico temprano para tratar los casos de manera inmediata evitando consecuencias fatales. En relaci&oacute;n a los casos cr&oacute;nicos, la afluencia promedio de usuarios en el per&iacute;odo estudiado (2013-2016) es de 879 personas/a&ntilde;o resultando entre 11-15% los positivos al diagn&oacute;stico. Estos se detectan principalmente en personas &ldquo;picadas por chipos&rdquo;, en cardi&oacute;patas y en el grupo mayor de 50 a&ntilde;os en quienes la positividad es del 25% de los usuarios, diagn&oacute;stico tard&iacute;o cuando el beneficio del tratamiento anti-parasitario es pr&aacute;cticamente nulo. La data de los pacientes cr&oacute;nicos no aporta indicaci&oacute;n de trasmisi&oacute;n en grupos vulnerables como ni&ntilde;os y embarazadas, pues el n&uacute;mero de usuarios es muy bajo. Es necesario incorporar el diagn&oacute;stico de la ECh en protocolos de rutina varios s&iacute;ndromes cl&iacute;nicos (fiebre prolongada, derrame peric&aacute;rdico), en pacientes inmunosuprimidos, embarazadas, ni&ntilde;os, conscriptos, programas de trasplantes, entre otras. Es urgente considerar la encuesta nacional de serolog&iacute;a de ECh en el grupo etario de 5 a 20 a&ntilde;os