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dc.contributor.authorTheys, Kristofen_US
dc.contributor.authorDeforche, Koenen_US
dc.contributor.authorVercauteren, Jurgenen_US
dc.contributor.authorLibin, Pieteren_US
dc.contributor.authorvan de Vijver, David A. M. C.en_US
dc.contributor.authorAlbert, Janen_US
dc.contributor.authorÅsjø, Birgittaen_US
dc.contributor.authorBalotta, Claudiaen_US
dc.contributor.authorBruckova, Marieen_US
dc.contributor.authorCamacho, Ricardo J.en_US
dc.contributor.authorClotet, Bonaventuraen_US
dc.contributor.authorCoughlan, Suzieen_US
dc.contributor.authorGrossman, Zehavaen_US
dc.contributor.authorHamouda, Osamahen_US
dc.contributor.authorHorban, Andrzeien_US
dc.contributor.authorKorn, Klausen_US
dc.contributor.authorKostrikis, Leondios G.en_US
dc.contributor.authorKücherer, Claudiaen_US
dc.contributor.authorNielsen, Clausen_US
dc.contributor.authorParaskevis, Dimitriosen_US
dc.contributor.authorPoljak, Marioen_US
dc.contributor.authorPuchhammer-Stockl, Elisabethen_US
dc.contributor.authorRiva, Chiaraen_US
dc.contributor.authorRuiz, Lidiaen_US
dc.contributor.authorLiitsola, Kirsien_US
dc.contributor.authorSchmit, Jean-Claudeen_US
dc.contributor.authorSchuurman, Roben_US
dc.contributor.authorSönnerborg, Andersen_US
dc.contributor.authorStanekova, Danicaen_US
dc.contributor.authorStanojevic, Majaen_US
dc.contributor.authorStruck, Danielen_US
dc.contributor.authorVan Laethem, Kristelen_US
dc.contributor.authorWensing, Annemarie M. J.en_US
dc.contributor.authorBoucher, Charles A. B.en_US
dc.contributor.authorVandamme, Anne-Miekeen_US
dc.contributor.authoron behalf of the SPREAD-programmeen_US
dc.description.abstractBackground: 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-relatedmutations in reverse transcriptase could not explain viral load or CD4 cell count variability.en_US
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.titleTreatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patientsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2012 Theys et al; licensee BioMed Central Ltd
dc.rights.holderKristof Theys et al.; licensee BioMed Central Ltd.

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