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      HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paraná, Brazil

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          Abstract

          Antiretroviral therapy (ART) has reduced morbidity and mortality related to human immunodeficiency virus (HIV) infection, but in spite of this advance, HIV mutations decrease antiretroviral susceptibility, thus contributing to treatment failure in patients. Genotyping HIV-1 allows the selection of new drugs after initial drug failure. This study evaluated the genotypic profile of HIV-1 isolates from treated (drug-experienced) patients in Paraná, Brazil. The prevalence of mutations in reverse transcriptase (RT) and protease (PR) genes were assessed. We analyzed 467 genotypes of patients with HIV-1 viral loads above 1,000 copies/mL. Mutations at HIV-1 RT and PR genes and previously used ART regimens were recorded. The most prevalent RT mutations were: 184V (68.31%), 215YF (51.6%), 103NS (46%), 41L (39.4%), 67N (38.54%), 210W (23.5%), 190ASE (23.2%), and 181C (17.4%). PR mutations were 90M (33.33%), 82ATFS (29%), 46I (26.8%) and 54V (22.2%). The prevalence of mutations was in line with previous national and international reports, except to nonnucleoside analogue reverse transcriptase inhibitors related mutations, which were more prevalent in this study. Previous exposure to antiretroviral drugs was associated with genotypic resistance to specific drugs, leading to treatment failure in HIV patients.

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          Most cited references55

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          EASL Clinical Practice Guidelines: management of chronic hepatitis B.

          (2009)
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            HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.

            J M Coffin (1995)
            Several recent reports indicate that the long, clinically latent phase that characterizes human immunodeficiency virus (HIV) infection of humans is not a period of viral inactivity, but an active process in which cells are being infected and dying at a high rate and in large numbers. These results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual. This turnover drives both the pathogenic process and (even more than mutation rate) the development of genetic variation. This variation includes the inevitable and, in principle, predictable accumulation of mutations such as those conferring resistance to antiviral drugs whose presence before therapy must be considered in the design of therapeutic strategies.
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              Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing.

              In a sample of 6,156 sequences from 4,183 persons, the top 30 patterns of protease inhibitor, nucleoside reverse transcriptase (RT) inhibitor, and nonnucleoside RT inhibitor mutations accounted for 55, 46, and 66%, respectively, of sequences with drug resistance mutations. Characterization of the phenotypic and clinical significance of these common patterns may lead to improved treatment recommendations for a large proportion of patients for whom antiretroviral therapy is failing.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                bjid
                Brazilian Journal of Infectious Diseases
                Braz J Infect Dis
                Brazilian Society of Infectious Diseases (Salvador )
                1678-4391
                August 2010
                : 14
                : 4
                : 360-371
                Affiliations
                [1 ] Universidade Federal do Paraná Brazil
                [2 ] Centro de Medicamentos do Paraná Brazil
                [3 ] Universidade Federal do Rio de Janeiro Brazil
                Article
                S1413-86702010000400009
                10.1590/S1413-86702010000400009
                3c9cd5ba-00f5-4aab-9d30-88c158354ecc

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=1413-8670&lng=en
                Categories
                INFECTIOUS DISEASES

                Infectious disease & Microbiology
                HIV-1,genotype,antiretrovirals,drug-experienced patients
                Infectious disease & Microbiology
                HIV-1, genotype, antiretrovirals, drug-experienced patients

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