TY - JOUR
T1 - HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen
AU - Cavaco-Silva, Joana
AU - Abecasis, Ana
AU - Miranda, Ana Cláudia
AU - Poças, José
AU - Narciso, Jorge
AU - Águas, Maria João
AU - Maltez, Fernando
AU - Almeida, Isabel
AU - Germano, Isabel
AU - Diniz, António
AU - Gonçalves, Maria De Fátima
AU - Gomes, Perpétua
AU - Cunha, Celso
AU - Camacho, Ricardo Jorge
N1 - Funding Information:
The authors have read the journal's policy and have the following conflicts: This study was funded by an unrestricted research grant provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. Data collected and views expressed in this article are the independent responsibility of the authors, with no conflict of interest to declare with the sponsor company nor with related marketed or in development products. Ricardo Camacho has previously received honoraria from MSD, a subsidiary of Merck & Co., Inc., as a consultant. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. The remaining authors of this article do not have any financial or personal relationships with people or organizations that could inappropriately influence this work.
PY - 2014/3/28
Y1 - 2014/3/28
N2 - To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTImajor resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.
AB - To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTImajor resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.
UR - http://www.scopus.com/inward/record.url?scp=84899857420&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0092747
DO - 10.1371/journal.pone.0092747
M3 - Article
C2 - 24681625
AN - SCOPUS:84899857420
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e92747
ER -