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Study of molecular resistance of human immunodeficiency virus (HIV-1) to antiretroviral drugs

By Εμμανουήλ Μαγιορκίνης

Abstract

The introduction of highly active antiretroviral therapy in clinical practice (HAART) increased the life expectancy and life quality of HIV-infected patients. However, the emergence of resistance is one of the main causes of antiretroviral treatment failure. Resistance to antiretroviral drugs is connected with the emergence of mutations in the genes that are targets of antiretroviral therapy, the protease, reverse transcriptase, integrase and gp41. Studies in antiretroviral drug resistance focus on patients receiving antiretroviral therapy in order to define patterns of drug resistance in new drugs or combinations of existing antiretrovirals, as well as on naive patients. The purpose of this study was to estimate the prevalence of HIV drug resistance in Greek naive HIV-infected individuals diagnosed in different time periods (<1999, 1999-2002, 2002-2003), the estimate of patterns of resistance in patients failing TDF-based therapies, the indentification of mutations predicting failure to TDF based regimens and the investigation of interesting cases of peculiar resistance profiles. Studies in HIV naive patients estimated the prevalence of resistance, in chronically infected patients diagnosed positive before 1999 and during 1999-2002 and in newly-diagnosed patients during the period 2002-2003 at 9%, whereas we were able to identify cases of transmission of HIV drug resistance through sexual intercourse. Studies in patients receiving TDF based regimens pointed out new positions (codons 123 and 196 in the reverse transcriptase region) which can predict response to TDF-based regimens by week 24, as well as new mutations at codon 70 (K70G, K70N) associated with failure to such regimens. Finally, we were able to identify and investigate, for the first time in international literature, a case of a NNRTI naive patient of the rare subtype CRF14_BG who developed an NNRTIassociated mutation.

Topics: Μοριακή αντοχή, Αντιρετροϊικά φάρμακα, Ανθεκτικότητα, Επιδημιολογία, Molecular resistance, HIV, AIDS νόσος, Antiretroviral drugs, Resistance, Epidemiology
Publisher: National and Kapodistrian University of Athens
Year: 2009
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