Resistance analyses in highly experienced patients failing raltegravir, etravirine and darunavir/ritonavir regimen

Charpentier, Charlotte, Roquebert, Bénédicte, Colin, Céline, Taburet, Anne-Marie, Fagard, Catherine, Katlama, Christine, Molina, Jean-Michel, Jacomet, Christine, Brun-Vézinet, Françoise, Chêne, Geneviève, Yazdanpanah, Yazdan, Descamps, Diane, The ANRS 139 TRIO Trial study group, and Fisher, Martin (2010) Resistance analyses in highly experienced patients failing raltegravir, etravirine and darunavir/ritonavir regimen. AIDS, 24 (17). pp. 2651-2656. ISSN 0269-9370

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Abstract

OBJECTIVES

ANRS 139 TRIO trial was a phase II noncomparative trial that evaluated in highly experienced patients, a combination of raltegravir, etravirine and darunavir boosted with ritonavir. We analyzed emergence of resistant viruses at the time of virological failure and investigated the impact of baseline integrase polymorphisms on virological failure occurrence.

METHODS

Bulk sequencing of protease, reverse transcriptase and integrase genes was performed for 103 patients at baseline and 14 patients at the time of virological failure. Additionally, integrase clonal analyses were performed at baseline and at virological failure in patients with successful integrase gene amplification. Impact of baseline integrase polymorphisms on virological failure occurrence was analyzed using Fisher exact and Wilcoxon tests.

RESULTS

In the 14 failing patients median viral load at virological failure was 90 copies/ml (interquartile range = 60-783). Emergence of darunavir and etravirine resistance mutations was observed at virological failure in only one and three patients, respectively. Raltegravir resistance mutations were found neither at baseline nor at the time of virologic failure. Integrase clonal analyses showed neither the presence nor the selection of minority variants carrying raltegravir resistance mutations at baseline or at virological failure. No impact of baseline integrase polymorphisms was observed on virological failure either at week 24 or at week 48.

CONCLUSION

Virological failure occurred in a small proportion of patients with low viral load. No raltegravir resistance mutations were observed using bulk sequencing or clonal analyses, and darunavir and etravirine resistance-associated mutations were detected in only one and three patients, respectively at virological failure. No impact of baseline integrase polymorphism was observed on virological failure occurrence.

Item Type: Article
Additional Information: Martin Fisher is not a named author of this article but is a member of The ANRS 139 TRIO Trial study group.
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine > RA0643 Communicable diseases and public health > RA0644 Individual diseases or groups of diseases, A-Z > RA0644.A25 AIDS. HIV infections
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Depositing User: Ellen Thomas
Date Deposited: 07 Apr 2014 13:29
Last Modified: 07 Apr 2014 13:29
URI: http://sro.sussex.ac.uk/id/eprint/48145
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