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Analysis of HIV-1 minority populations resistant to the non-nucleoside reverse transcriptase inhibitor (NNRTI) Etravirine among patients infected with HIV-1 resistant to the NNRTIs nevirapine and Efavirenz

Grant number: 12/24799-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2013
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Ricardo Sobhie Diaz
Grantee:Thiago de Matos Dourado
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The Highly Active Antiretroviral Therapy (HAART) has been shown great results. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used as first line therapy. In Brazil, the therapy comprises the first generation NNRTIs, nevirapina and efavirenz, and also the second generation NNRTI, etravirine. These drugs change the HIV-1 reverse transcriptase conformation, alteration that inactivates the ability of retrotranscription. However, the mutagenic capacity of HIV has provided an obstacle for aids therapy. One characteristic of this class of antiretrovirals is the development of cross-resistance. Therefore, when a mutation in codons related to NNRTIs susceptibility occurs, normally, all first-generation NNRTIs have the susceptibility reduced. This study aims to verify the hypothesis of selection of resistant populations of HIV-1 for the second-generation NNRTI, etravirine, in response to the selective pressure exerted by first-generation NNRTIs among patients with HIV-1 resistant to nevirapine or efavirenz. The study will examine the difference between virions in plasma and provirus in the subtypes B and C. However, conventional techniques are incapable of detecting sequence variants which have frequencies below 20-30%. In this study, we will use the ultra-deep sequencing, a more sensitive technique (1% for minority populations) that provides greater efficiency to estimate the resistance prevalence.