Genetic analysis of protease and reverse transcriptase of HIV-1 from Southern Brazil naïve clinical isolates

Abstract

Background: Rio Grande do Sul, the southernmost state of Brazil, presents an atypical epidemiological situation where HIV-1 subtype C co-circulates with subtypes B and CRF31_BC, contrasting with the other Brazilian regions were subtypes B and F dominates. These infections have been effectively managed with highly active antiretroviral therapy (HAART) since 1996. Objective: To evaluate the profile of mutations and polymorphisms in the protease and reverse transcriptase regions in diferent subtypes of HIV-1 from untreated patients living in Southern Brazil. Methods: Blood samples from 99 HIV-1 positive antiretroviral/drugs-naïve, which were not in drug therapy, were collected from 2005 to 2007, in Porto Alegre Brazil. Protease and reverse transcriptase genes were amplified, sequenced and subtyped through phylogenetic analyses. HIV strain genotyping was performed by partial pol sequence analysis with the HIV Drug Resistance Database of Stanford University. Results: Phylogenetic analyses of the 99 pol samples, were classified according their subtypes: B (26.2%), C (39.4%), F (1.1%), CRF31_CB (19.2%) and URF (14.1%). Eight (8.1%) samples showed primary resistance mutations to Calibrated Population Resistance tool based in the 2009 Surveillance Drug Resistance Mutation list. Two samples presented PI resistance mutations: I54T and I54L; two NRTI resistance mutation: D67G, D67N and K70R, and three NNRTI resistance mutation: V106M, Y181C and K103N. There is no significant association between presence of resistant genotypes and subtypes, but resistance mutations seem to be less frequent at subtype C. Conclusions: Primary resistance mutations represented 8.1% of sequences demonstrating an increase of 5% in the last years in that region. Here, we describe for the first time the mutational profile of CRF31_BC. In this light, the results of genetic analysis of HIV-1 from naïve patients appear to be a promising and important tool for the surveillance of HIV infection.