Gene expression before HAART initiation predicts HIV-infected individuals at risk of poor CD4+ T-cell recovery

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Objective:To identify a pre-HAART gene expression signature in peripheral blood mononuclear cells (PBMCs) predictive of CD4+ T-cell recovery during HAART in HIV-infected individuals.Design:This retrospective study evaluated PBMC gene expression in 24 recently HIV-infected individuals before the initiation of HAART to identify genes whose expression is predictive of CD4+ T-cell recovery after 48 weeks of HAART.Methods:The change in CD4+ T-cell count (ΔCD4) over the 48-week study period was calculated for each of the 24 participants. Twelve participants were assigned to the ‘good’ (ΔCD4 ≥ 200 cells/μl) and 12 to the ‘poor’ (ΔCD4 < 200 cells/μl) CD4+ T-cell recovery group. Gene expression profiling of the entire transcriptome using Illumina BeadChips was performed with PBMC samples obtained before HAART. Gene expression classifiers capable of predicting CD4+ T-cell recovery group (good vs. poor), as well as the specific ΔCD4 value, at week 48 were constructed using methods of Class Prediction.Results:The expression of 40 genes in PBMC samples taken before HAART predicted CD4+ T-cell recovery group (good vs. poor) at week 48 with 100% accuracy. The expression of 22 genes predicted a specific ΔCD4 value for each HIV-infected individual that correlated well with actual values (R = 0.82). Predicted ΔCD4 values were also used to assign individuals to good vs. poor CD4+ T-cell recovery groups with 79% accuracy.Conclusion:Gene expression in PBMCs can be used as biomarkers to successfully predict disease outcomes among HIV-infected individuals treated with HAART.

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