دورية أكاديمية
Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients.
| العنوان: | Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients. |
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| المؤلفون: | Theys, Kristof, Deforche, Koen, Vercauteren, Jurgen, Libin, Pieter, van de Vijver, David Amc, Albert, Jan, Asjo, Birgitta, Balotta, Claudia, Bruckova, Marie, Camacho, Ricardo J., Clotet, Bonaventura, Coughlan, Suzie, Grossman, Zehava, Hamouda, Osamah, Horban, Andrzei, Korn, Klaus, Kostrikis, Leondios G., Kucherer, Claudia, Nielsen, Claus, Paraskevis, Dimitrios, Poljak, Mario, Puchhammer-Stockl, Elisabeth, Riva, Chiara, Ruiz, Lidia, Liitsola, Kirsi, Schmit, Jean-Claude, Schuurman, Rob, Sonnerborg, Anders, Stanekova, Danica, Stanojevic, Maja, Struck, Daniel, Van Laethem, Kristel, Wensing, Annemarie Mj, Boucher, Charles Ab, Vandamme, Anne-Mieke, MOUTSCHEN, Michel |
| المصدر: | Retrovirology, 9, 81 (2012) |
| بيانات النشر: | Springer |
| سنة النشر: | 2012 |
| المجموعة: | University of Liège: ORBi (Open Repository and Bibliography) |
| مصطلحات موضوعية: | Human health sciences, Immunology & infectious disease, Sciences de la santé humaine, Immunologie & maladie infectieuse |
| الوصف: | peer reviewed ; BACKGROUND: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. RESULTS: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. CONCLUSIONS: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1742-4690 |
| العلاقة: | urn:issn:1742-4690; https://orbi.uliege.be/handle/2268/158776Test; info:hdl:2268/158776; https://orbi.uliege.be/bitstream/2268/158776/1/1742-4690-9-81.pdfTest; scopus-id:2-s2.0-84866850986; info:pmid:23031662 |
| DOI: | 10.1186/1742-4690-9-81 |
| الإتاحة: | https://doi.org/10.1186/1742-4690-9-81Test https://orbi.uliege.be/handle/2268/158776Test https://orbi.uliege.be/bitstream/2268/158776/1/1742-4690-9-81.pdfTest |
| حقوق: | open access ; http://purl.org/coar/access_right/c_abf2Test ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.C5E887CA |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17424690 |
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| DOI: | 10.1186/1742-4690-9-81 |