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 Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2013
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ricardo Sobhie Diaz
• Grantee: Thiago de Matos Dourado
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Highly Active Antiretroviral Therapy (HAART) has been shown great results. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used as first-line therapy. In Brazil, the therapy comprises the first-generation NNRTIs, nevirapine, and efavirenz, and also the second-generation NNRTI, etravirine. These drugs change the HIV-1 reverse transcriptase conformation, an 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 that have frequencies below 20-30%. In this study, we will use ultra-deep sequencing, a more sensitive technique (1% for minority populations) that provides greater efficiency to estimate the resistance prevalence. (AU)