Genotypic prediction of tropism of highly diverse HIV-1 strains from Cameroon

喀麦隆 HIV-1 高度多样化毒株趋向性的基因型预测

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作者:Christelle Mbondji-Wonje, Viswanath Ragupathy, Jiangqin Zhao, Aubin Nanfack, Sherwin Lee, Judith Torimiro, Phillipe Nyambi, Indira K Hewlett

Background

The use of CCR5 antagonists involves determination of HIV-1 tropism prior to initiation of treatment. HIV-1 tropism can be assessed either by phenotypic or genotypic

Conclusion

Our study demonstrated that overall, genotypic methods were less sensitive for accurate prediction of HIV-1 tropism in settings where diverse HIV-1 strains co-circulate. Our data suggest that further optimization of genotypic methods is needed and that larger studies to determine their utility for tropism prediction of diverse HIV-1 strains may be warranted.

Methods

Tropism of diverse HIV-1 strains isolated from PBMCs from Cameroon was determined using the GHOST cell assay. Prediction, based on V3 sequences from matched plasma samples, was determined using bioinformatics algorithms and rules based on position 11/25 and net charge applied independently or combined according to Delobel's and Garrido's rules. Performance of genotypic methods was evaluated by comparing prediction generated with tropism assigned by the phenotypic assay.

Results

Specificity for predicting R5-tropic virus was high, ranging from 83.7% to 97.7% depending on the genotypic methods used. Sensitivity for X4-tropic viruses was fairly low, ranging from 33.3% to 50%. In our study, overall, genotypic methods were less able to accurately predict X4-tropic virus belonging to subtype CRF02_AG. In addition, it was found that of the methods we used the Garrido rule has the highest sensitivity rate of over 50% with a specificity of 93%.

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