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Báo cáo y học: " The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage? | Wiesmann et al. AIDS Research and Therapy 2011 8 7 http www.aidsrestherapy.eom content 8 1 7 AIDS RESEARCH AND THERAPY SHORT REPORT Open Access The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir is there a clinical advantage 1 1 1 2 3 4 5 Frank Wiesmann Jan Vachta Robert Ehret Hauke Walter Rolf Kaiser Martin Sturmer André Tappe Martin Daumer6 Thomas Berg7 Gudrun Naeth1 Patrick Braun1 Heribert Knechten1 Abstract Background Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations. Results Based on a cohort of 47 L76V-positive patients we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options. Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir Saquinavir Amprenavir and Lopinavir were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype Virco . The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks. Conclusions In this analysis the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact a clear benefit in drug susceptibility for these drugs was .