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Antiviral Resistance and Correlates of Virologic Failure in the first Cohort of HIV-Infected Children Gaining Access to Structured Antiretroviral Therapy in Lima, Peru: A Cross-Sectional Analysis

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dc.contributor.author Rath, Barbara A.
dc.contributor.author von Kleist, Max
dc.contributor.author Castillo, Maria E.
dc.contributor.author Kolevic, Lenka
dc.contributor.author Caballero, Patricia
dc.contributor.author Soto-Castellares, Giselle
dc.contributor.author Amedee, Angela M.
dc.contributor.author Robinson, James E.
dc.contributor.author Katzenstein, David K.
dc.contributor.author Van Dyke, Russell B.
dc.contributor.author Oberhelman, Richard A.
dc.date.accessioned 2022-01-04T20:29:55Z
dc.date.available 2022-01-04T20:29:55Z
dc.date.issued 2013
dc.identifier.uri https://hdl.handle.net/20.500.12866/10398
dc.description.abstract Background: The impact of extended use of ART in developing countries has been enormous. A thorough understanding of all factors contributing to the success of antiretroviral therapy is required. The current study aims to investigate the value of cross-sectional drug resistance monitoring using DNA and RNA oligonucleotide ligation assays (OLA) in treatment cohorts in low-resource settings. The study was conducted in the first cohort of children gaining access to structured ART in Peru. Methods: Between 2002–5, 46 eligible children started the standard regimen of AZT, 3TC and NFV Patients had a median age of 5.6 years (range: 0.7-14y), a median viral load of 1.7·105 RNA/ml (range: 2.1·103 – 1.2·106), and a median CD4-count of 232 cells/μL (range: 1–1591). Of these, 20 patients were classified as CDC clinical category C and 31/46 as CDC immune category 3. At the time of cross-sectional analysis in 2005, adherence questionnaires were administered. DNA OLAs and RNA OLAs were performed from fro en PBMC and plasma, RNA genotyping from dried blood spots. Results: During the first year of ART, 44% of children experienced virologic failure, with an additional 9% failing by the end of the second year. Virologic failure was significantly associated with the number of resistance mutations detected by DNA-OLA (p < 0.001) during cross-sectional analysis, but also with low immunologic CDC-scores at baseline (p < 0.001). Children who had been exposed to unsupervised short-term antiretrovirals before starting structured ART showed significantly higher numbers of resistance mutations by DNA-OLA (p = 0.01). Detection of M184V (3TC resistance) by RNA-OLA and DNA-OLA demonstrated a sensitivity of 0.93 and 0.86 and specificity of 0.67 and 0.7, respectively, for the identification of virologic failure. The RT mutations N88D and L90M (NFV resistance) detected by DNA-OLA correlated with virologic failure, whereas mutations at RT position 215 (AZT resistance) were not associated with virologic failure. Conclusions: Advanced immunosuppression at baseline and previous exposures to unsupervised brief cycles of ART significantly impaired treatment outcomes at a time when structured ART was finally introduced in his cohort. Brief maternal exposures to with AZT +/− NVP for the prevention of mother-to-child transmission did not affect treatment outcomes in this group of children. DNA-OLA from frozen PBMC provided a highly specific tool to detect archived drug resistance. RNA consensus genotyping from dried blood spots and RNA-OLA from plasma consistently detected drug resistance mutations, but merely in association with virologic failure. en_US
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartofseries BMC Infectious Diseases
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Cross-Sectional Studies en_US
dc.subject human en_US
dc.subject Peru en_US
dc.subject questionnaire en_US
dc.subject sensitivity and specificity en_US
dc.subject HIV Infections en_US
dc.subject Human immunodeficiency virus infection en_US
dc.subject treatment outcome en_US
dc.subject human cell en_US
dc.subject antiretrovirus agent en_US
dc.subject cohort analysis en_US
dc.subject Human immunodeficiency virus infected patient en_US
dc.subject CD4 lymphocyte count en_US
dc.subject genotype en_US
dc.subject article en_US
dc.subject antiviral therapy en_US
dc.subject CD4 Lymphocyte Count en_US
dc.subject HIV-1 en_US
dc.subject clinical article en_US
dc.subject Antiretroviral Therapy, Highly Active en_US
dc.subject genetic analysis en_US
dc.subject genetic association en_US
dc.subject drug exposure en_US
dc.subject treatment duration en_US
dc.subject immunosuppressive treatment en_US
dc.subject drug treatment failure en_US
dc.subject virus RNA en_US
dc.subject vertical transmission en_US
dc.subject RNA en_US
dc.subject peripheral blood mononuclear cell en_US
dc.subject health care access en_US
dc.subject DNA en_US
dc.subject disease classification en_US
dc.subject Treatment Failure en_US
dc.subject Mutation en_US
dc.subject dried blood spot testing en_US
dc.subject virus load en_US
dc.subject Disease Progression en_US
dc.subject Viral Load en_US
dc.subject antiviral resistance en_US
dc.subject blood analysis en_US
dc.subject consensus sequence en_US
dc.subject drug monitoring en_US
dc.subject Drug Resistance, Viral en_US
dc.subject Genes, Viral en_US
dc.subject lamivudine en_US
dc.subject nelfinavir en_US
dc.subject oligonucleotide ligation assay en_US
dc.subject virus mutation en_US
dc.subject zidovudine en_US
dc.title Antiviral Resistance and Correlates of Virologic Failure in the first Cohort of HIV-Infected Children Gaining Access to Structured Antiretroviral Therapy in Lima, Peru: A Cross-Sectional Analysis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1186/1471-2334-13-1
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.relation.issn 1471-2334


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