Association of Gag cleavage sites to protease mutations and to virological response in HIV-1 treated patients
| Autor: | Vincent Calvez, Rachid Agher, Bénédicte Roquebert, Marc Wirden, Anne-Geneviève Marcelin, Dominique Costagliola, Anne Simon, Bahia Amellal, Christine Katlama, Cécile Dalban, Isabelle Malet |
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| Rok vydání: | 2007 |
| Předmět: |
Microbiology (medical)
Anti-HIV Agents viruses medicine.medical_treatment Molecular Sequence Data Gene Products gag HIV Infections Drug resistance Biology HIV Protease Immunopathology Drug Resistance Viral medicine Humans Amino Acid Sequence Sida Peptide sequence Saquinavir Binding Sites Ritonavir Protease HIV Protease Inhibitors biology.organism_classification Virology Treatment Outcome Infectious Diseases Mutation HIV-1 Viral disease medicine.drug |
| Zdroj: | Journal of Infection. 54:367-374 |
| ISSN: | 0163-4453 |
| Popis: | Summary Objectives The sequence variability in the protease and in the 5 Gag cleavage sites (CS) were explored to look for eventual associations between the mutations. Moreover, we have evaluated associations between the Gag region sequence and the virological response to Protease Inhibitors (PI). Methods The protease and the 5 Gag CS sequences from 98 PI-experienced patients were sequenced and compared to the HXB2 reference sequence. Sixty patients, treated by Saquinavir plus Ritonavir, were studied to evaluate the clinical impact of the Gag region variability. Results The relationship between 63 protease mutations and 21 Gag CS mutations were explored. Two patterns of mutations in the protease were identified: (M46I/L, I54V, V82A/T/F) was associated to the A431V and (K20I/R/M, L89M/I) to the S373Q and L449P. None of the Gag CS mutations resulting from PI treatment was associated to the virological response to SQV/r. On the other hand, the S373P mutation had a negative impact on the virological response that remained statistically significant in a multivariate analysis after adjustment on the number of PI resistance mutations. Conclusions These results evoke the pertinence to introduce some mutations found in the Gag CS in the algorithms used for the interpretation of resistance testing. |
| Databáze: | OpenAIRE |
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