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

Abstract

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.