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19952713
Gene expression before HAART initiation predicts HIV-infected individuals at risk of poor CD4+ T-cell recovery.

AIDS, 2010/1/16;24(2):217-22.

Woelk CH[1], Beliakova-Bethell N, Goicoechea M, Zhao Y, Du P, Rought SE, Lozach J, Pérez-Santiago J, Richman DD, Smith DM, Little SJ

Affiliations

PMID: 19952713DOI: 10.1097/QAD.0b013e328334f1f0

Impact factor: 4.632

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.
MeSH terms
Adult; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Gene Expression; Gene Expression Profiling; HIV Infections; HIV-1; Humans; Immunity, Cellular; Male; Prognosis; Retrospective Studies; Time Factors
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