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

Woelk, Christopher Ha,b; Beliakova-Bethell, Nadejdac; Goicoechea, Miguela; Zhao, Yingdongd; Du, Pinyia; Rought, Steffney Ea; Lozach, Jeane; Pérez-Santiago, Josuéa; Richman, Douglas Da,b,c; Smith, Davey Ma,b; Little, Susan Ja

doi: 10.1097/QAD.0b013e328334f1f0
Basic Science: Concise Communications

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.

aDepartment of Medicine, University of California San Diego, La Jolla, USA

bVeterans Affairs San Diego Healthcare System, San Diego, USA

cDepartment of Pathology, University of California San Diego, La Jolla, California, USA

dBiometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Rockville, Maryland, USA

eIllumina Inc., San Diego, California, USA.

Received 21 August, 2009

Revised 12 October, 2009

Accepted 4 November, 2009

Correspondence to Christopher H. Woelk, Assistant Professor, Department of Medicine, University of California San Diego, Stein Clinical Research Building, Room 326, 9500 Gilman Drive 0679, La Jolla, CA 92093-0679, USA. Tel: +1 858 552 8585x7193; fax: +1 858 552 7445; e-mail: cwoelk@ucsd.edu

© 2010 Lippincott Williams & Wilkins, Inc.