Differential Evolution of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Genes Between HAART-Failing and Naive- Treated Individuals

Rafael   B.   Varella; Carlos   G.   Schrago; Mariano   G.   Zalis

doi:10.2174/157016209789973664

Abstract

We described differential selective pressures along codon sites of the RT and PR genes of HIV-1 from HAART-failing and naive-treated individuals, through the comparison of the ratio of non-synonymous mutations (dN) to synonymous mutations (dS) substitution per site. Resistance-associated mutations were found in 1/71 (1.4%) and 109/117 (93.1%) samples from naive-treated and HAART-failing individuals, respectively, although most of positively selected codons represented polymorphisms in positions 123, 211, 245, 297 in RT and 37, 63 in PR of naive-treated samples and positions 122, 123, 245, 272, 277, 286, 297 in RT and 10, 15, 20, 35, 37, 62, 63, 64, 71, 72, 77, 93 in PR of HAARTfailing samples, except by ARV-resistance codons 74, 184, 215 in RT and 90 in PR exclusively found in HAART-failing group. The number and diversity of sites under selective pressure at populational level also increased in RT but not in PR of treated individuals. Our results demonstrated no evolution of drug-associated codons among untreated individuals, indicating unlikely transmission and adaptation of resistant HIV-1 strains in a free drug environment. Polymorphic sites observed exclusively in HAART-failing group, may contribute to HIV-1 escape and adaptation at individual and populational levels in a drug environment, although those mutually found in HIV-1 despite of previous exposure to ARV treatment, should not be considered accurate resistance markers.

Keywords: HIV-1, protease, reverse transcriptase, resistance, HAART

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