Insertions and deletions at the HIV-1 polymerase in patients on HAART at the Public Health System of Sao Paulo State, Brazil
L.O. Souza, G.I.S. Lopez Lopes, K.P. Barroso, J.P.G. Batista, R.B. Andrade, L.F.M. Brígido
Instituto Adolfo Lutz, Serviço de Virologia - Laboratório de Genotipagem do HIV, São Paulo, Brazil
Background: Insertion and deletion (indels) are mechanisms of viral escape and may involve one or more amino acids (aa). The most described indels at polymerase are at codon 35PR and 69RT, generally associated to resistance to ARTs. Insertions are associated to duplication of nearby fragments. The aim of this study is to describe indels in the PR and RT of HIV-1 among patients failing HAART.
Methods: We analyzed 1703 sequences from patient´s failing ARV therapy from Sao Paulo State - Brazil, from 2004 to 2009, collected for resistance test. The sequences were edited manually and analyzed by the Stanford algorithm (http://hivdb.stanford.edu/) HIV Drug Resistance Database to confirm the location of the mutations.
Results: The frequency of RT insertion was 16/1703 (1%). In all cases, insertion occurs in 69 codon. The inserted aa included N/T/D/VT/SS/SG and two samples of a same patient showed an insertion of 8 aa. In PR, we found 9/1703 (0.5%) samples with insertion, located between codons 33 and 37. The inserted aa were: L and LE (33); K/D/N/E/EN (35) and F (37). Deletions were identified in 8/1703 (0.5%). Of these, 6 deletions were in 67 codon and two in 69. No deletions were detected at PR.
Conclusions: Although the frequency of insertion and deletion events was similar to described in the literature, 69 VT insertion appear to have no been described so far. Different from Stanford database, the most common mutations observed at 69 were S. Inserts type SS and SG are reported with some frequency in literature. Our results suggest the most insertions are not duplication of adjacent sites. As insertions at the region 33 to 37 PR may not be associated to ARV therapy their evolution could be under the influence of additional selective pressure.
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