Accession Number:

ADA528211

Title:

CCL3L1-CCR5 Genotype Improves the Assessment of AIDS Risk in HIV-1-Infected Individuals

Descriptive Note:

Journal article

Corporate Author:

UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD

Report Date:

2008-09-08

Pagination or Media Count:

16.0

Abstract:

Background Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy HAART during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4 T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. Methods and Findings In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group GRG based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1- CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree CART analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4 cell count thresholds used to guide HAART initiation. Conclusions The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By track

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE