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


METHODS
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.


CONCLUSIONS
Gene expression in PBMCs can be used as biomarkers to successfully predict disease outcomes among HIV-infected individuals treated with HAART.
Woelk
Christopher H
CH
Department of Medicine, University of California, San Diego, La Jolla, USA. cwoelk@ucsd.edu
Beliakova-Bethell
Nadejda
N
Goicoechea
Miguel
M
Zhao
Yingdong
Y
Du
Pinyi
P
Rought
Steffney E
SE
Lozach
Jean
J
Pérez-Santiago
Josué
J
Richman
Douglas D
DD
Smith
Davey M
DM
Little
Susan J
SJ
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000821:virology; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors