Investigation of Baseline Susceptibility to Protease Inhibitors in HIV-1 Subtypes C, F, G and Crf02_Ag

Antiviral Therapy - Tập 11 Số 5 - Trang 581-589 - 2006
Ana Abecasis1,2, Koen Deforche1, Lee T. Bacheler3, Paula McKenna4, Jonathan Schapiro2, Perpétua Gómes2, Anne‐Mieke Vandamme1, Ricardo Camacho1,4,3,2
1Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
2Virology Laboratory, Hospital Egas Moniz, Lisbon, Portugal
3VircoLab Inc., Durham, NC, USA
4Virco BVBA, Mechelen, Belgium

Tóm tắt

Objective To compare baseline susceptibility to protease inhibitors among HIV-1 isolates of subtypes C, F, G and CRF02_AG, and to identify polymorphisms that determine the differences in susceptibility. Methods A total of 42 samples of drug-naive patients infected with subtypes G ( n=19), CRF02_AG ( n=10), F ( n=6) and C ( n=7) were phenotyped and genotyped with the Antivirogram and the ViroSeq 2.0 genotyping system, respectively. A Bayesian network approach was used for a preliminary analysis of the collected data and the dependencies indicated by the network were statistically confirmed. Results CRF02_AG samples were found to be more susceptible to nelfinavir and ritonavir than other subtypes. Hypersusceptibility to these drugs was associated with the 70R polymorphism. 37D/S/T was associated with reduced susceptibility to indinavir and 89M with reduced susceptibility to lopinavir. Susceptibility to tipranavir was the lowest among the subtype F samples and the highest for subtype G samples, with samples carrying 57R being more susceptible than samples carrying 57K. Conclusions Our study suggests that there are baseline susceptibility differences between subtypes and these differences are due to naturally occurring polymorphisms in these subtypes. The predictive value for phenotype of these polymorphisms was even valid in subtypes where these polymorphisms are less prevalent. Taking into account such polymorphisms should improve current algorithms for interpretation of genotyping results in a subtype-independent way.

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Antiviral Therapy

Tập 11 Số 5

581-589

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