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

Woelk, Christopher H., Beliakova-Bethell, Nadejda, Goicoechea, Miguel, Zhao, Yingdong, Du, Pinyl, Rought, Steffney E., Lozach, Jean, Pérez-Santiago, Josué, Richman, Douglas D. and Little, Susan J. (2010) Gene expression before HAART initiation predicts HIV-infected individuals at risk of poor CD4(+) T-cell recovery. AIDS, 24 (2), 217-222. (doi:10.1097/QAD.0b013e328334f1f0). (PMID:19952713)

Abstract

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 (DeltaCD4) over the 48-week study period was calculated for each of the 24 participants. Twelve participants were assigned to the 'good' (DeltaCD4 > or = 200 cells/microl) and 12 to the 'poor' (DeltaCD4 < 200 cells/microl) 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 DeltaCD4 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 DeltaCD4 value for each HIV-infected individual that correlated well with actual values (R = 0.82). Predicted DeltaCD4 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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