Azevedo, R Gonçalves

Castro, D Funayama

Diaz, R Sobhie

Komninakis, S Vasconcelos

Pena, N Mantovani

Journal of the International AIDS Society

English

PubMed

N Mantovani Pena

R Gonçalves Azevedo

D Funayama Castro

R Sobhie Diaz

S Vasconcelos Komninakis

Crossref

High levels of polymorphisms related to raltegravir resistance among raltegravir-naïve individuals in Brazil

N Pena

R Azevedo

D Castro

R Diaz

S Komninakis

Springer - Publisher Connector

POSTER PRESENTATION Open Access
High levels of polymorphisms related to
raltegravir resistance among raltegravir-naïve
individuals in Brazil
N Mantovani Pena1, R Gonçalves Azevedo1, D Funayama Castro2, R Sobhie Diaz1*, S Vasconcelos Komninakis1
From Tenth International Congress on Drug Therapy in HIV Infection
Glasgow, UK. 7-11 November 2010
Purpose of the study
Raltegravir (RAL) is an HIV-1 integrase strand-transfer
inhibitor that has exhibited substantial efficacy and a
favorable safety profile in HIV-1 infected patients. The
goal of this study was to explore the presence of natural
polymorphisms and primary mutations related to RAL
resistance among HIV-1 patients failing to multiple anti-
retroviral agents.
Methods
25 plasmas from HIV-1 infected patients with HAART
failure were studied. Genetic analysis was performed
amplifying and sequencing DNA encompassing 288
amino acids of HIV-1 integrase gene. Drug resistance
mutations and polymorphisms were examined following
Low et al, 2009. Genetic subtypes were analyzed using
REGA HIV Subtyping Tool (http://www.bioafrica.net/
subtypetool/html/subtypinghiv.html).
Results
Of the 25 patients, 15 were males and 10 females. All of
them are more than 18 years old and 19 patients born
in Sao Paulo city. 22 patients were infected by HIV-1
subtype B, 1 by subtype F and 2 by B/F recombinants.
No Raltegravir resistance related mutations were
observed, however we identified following polymorph-
isms: V72I (44%), T97A (4%), Q146K (4%), V151I (28%),
V201I (52%), T206S (8%), I203M (12%), S230N (4%),
M154L (4%), K156N (16%) e K156R (4%). Furthermore,
we observed amino acid substitutions at codons 163 in
two patients (G163E and G163V) and 138 in one patient
(E138N).
Conclusions
Despite the absence of RAL primary resistance muta-
tions, we found a high frequency of polymorphisms that
were related to in vitro reduced susceptibility to RAL.
Furthermore, substitutions at codons 163 (G163R) and
138 (E138K) are called secondary mutations, which are
capable to restore viral fitness due to the presence of
primary mutations. Further studies are needed to deter-
mine the importance of these polymorphisms in redu-
cing the genetic barrier to RAL resistance among
treated individuals.
Author details
1Federal University of São Paulo, São Paulo, Brazil. 2Lusiada Fundation of
Santos, Santos, Brazil.
Published: 8 November 2010
Reference
1. Low , et al: Antimicrobial Agents and Chemotherapy. 2009,
53(10):4275-4282, Oct. 2009.
doi:10.1186/1758-2652-13-S4-P135
Cite this article as: Pena et al.: High levels of polymorphisms related to
raltegravir resistance among raltegravir-naïve individuals in Brazil.
Journal of the International AIDS Society 2010 13(Suppl 4):P135.
1Federal University of São Paulo, São Paulo, Brazil
Full list of author information is available at the end of the article
Pena et al. Journal of the International AIDS Society 2010, 13(Suppl 4):P135
http://www.jiasociety.org/content/13/S4/P135
© 2010 Diaz et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.


Antimicrobial Agents and Chemotherapy.

Brazil Full list of author information is available at the end of the article Pena et al.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3112911

High levels of polymorphisms related to raltegravir resistance among raltegravir-naïve individuals in Brazil

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