Spatial-temporal analysis of HIV-1 PR and RT resistance-associated mutations of nucleotide sequences from Western Europe, using vircoTYPE™ HIV-1 assay

Autor: P Van den Eede, M Govaert, K Soom Van, J Villacian, Theresa Pattery
Rok vydání: 2012
Předmět:
Zdroj: Journal of the International AIDS Society. 15
ISSN: 1758-2652
DOI: 10.7448/ias.15.6.18171
Popis: Highly effective regimens have drastically improved HIV morbidity and mortality although anti-retro viral resistance remains a limiting factor in disease management. Therefore, analysis of large sequence datasets may provide better insight into drug resistance & assist policy makers to select optimized treatment strategies. Using a secure, web-based sequence submission tool (vircoNETTM, Janssen Diagnostics BVBA), centers within EU have been able to retrieve the CE-marked vircoTYPETM HIV-1 (VTY) genotyping reports for their patients. The purpose of this study is to perform a descriptive analysis of the prevalence of HIV-1 PR & RT resistance-associated mutations (RAMs) from submitted nucleotide sequences, collected during an 8 year period, from 5 West-European countries & Switzerland. From January 2005 - June 2012, 27,262 sequences were submitted via vircoNETTM & analyzed using VTY. Approximately 50% of the sequences were submitted from Spain (n=14120) & 24% from Italy (n=6415). The remaining sequences were from UK (n=2097), France (n=1508), Germany (n=1041) & Switzerland (n=2081). The majority (80%, 21,647/27,262) of the sequences were Clade B. For NRTI RAMs, M184V was the most prevalent mutation (36%, n=9944) followed by M41L (25%, n=6701). For NNRTI RAMs, K103N mutation was most prevalent (24%, n=6481) followed by Y181C (10% n=2704). For PIs, L90M (16%, n=4453) and M46I (12%, n=3397) were the most prevalent. The overall RAM prevalence has declined over the 8 year period. 7602 (28%) sequences had no major RAMs and were sensitive to all 18 FDA & EMA-approved drugs present on VTY. In the PI class, VTY predicted 95% (20097/21243) of the sequences as sensitive & 5% (1146/21243) resistant to darunavir, followed by tipranavir, lopinavir & saquinavir with equal sensitivity rate (SR) of 81% & a resistance rate (RR) of 13%, 18% & 19% respectively. In the NNRTI class, etravirine had a better SR (81%, 8628/10683) & RR (19%, 2055/10683) when compared to nevirapine and efavirenz, with a SR of 59% & RR of 41% for both drugs. For NRTIs, the highest SR was found for stavudine (77%, 20889/27262) followed by tenofovir (67%, 18249/27262) with 23% (6499/27262) resistant sequences observed for stavudine & 33% (9114/27262) for tenofovir. The current analysis provides some preliminary insight into HIV mutation pattern prevalence and resistance within Western Europe, suggesting good therapeutic opportunities for regimens containing new generation PIs & NNRTIs. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Van den Eede P et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18171 http://www.jiasociety.org/index.php/jias/article/view/18171 | http://dx.doi.org/10.7448/IAS.15.6.18171
Databáze: OpenAIRE