Changes in T Cell Receptor Excision DNA Circle (TREC) Levels in HIV Type 1-Infected Subjects Pre- and Post-Highly Active Antiretroviral Therapy

Abstract

The T cell receptor excision DNA circle (TREC) level is an independent predictor of HIV-1 disease prognosis. We studied the temporal changes in TREC levels prior to and after highly active antiretroviral therapy (HAART) in a cohort of 131 Greek men with hemophilia who were followed up for up to 20 years since seroconversion (SC). TREC levels were determined in all available cryopreserved samples of peripheral blood mononuclear cells (PBMCs) using a multiplex real-time polymerase chain reaction (PCR) assay. Trends in log 10 TREC values were described using random effects models. Prior to HAART initiation TREC levels tended to decrease over time (mean rate of drop 19% per year

95% CI: 16-22%). Initial TREC values were higher with younger age at SC, but the subsequent rate of drop did not differ significantly by age at SC. There was a monotonic relationship between baseline HIV-RNA levels and TREC slopes with steeper slopes at higher levels of HIV-RNA. The TREC slopes differed significantly by clinical outcome being steeper in subjects who progressed to AIDS sooner. After HAART initiation, TREC values tended to increase on average by 35% per year (95% CI: -7-94%) but the increase was evident only in subjects with a pre-HAART CD4 count below 80 cells/μl. TREC values, which likely represent a simple indicator of naive T-lymphocyte reserve, may be a clinically useful marker for long-term prognosis of HTV-1 infection and for immune reconstitution after successful HAART.