Factors influencing T-cell turnover in HIV-1-seropositive patients

HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method fo r endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disea se, the average half life of circulating T cells was diminished without com pensatory increases in cell production. Within 12 weeks of the initiation o f highly active antiretroviral therapy (HAART), the absolute production rat es of circulating T cells increased, and normal half-lives and production r ates were restored by 12-36 months. Interpatient heterogeneity in the absol ute degree of turnover correlated with the relative proportion of naive- an d memory/effector-phenotype T cells in each of the CD4+ and CD8+ population s. The half-lives of naive-phenotype T cells ranged from 116-365 days (frac tional replacement rates of 0.19-0.60% per day), whereas memory/effector-ph enotype T cells persisted with half-lives from 22-79 days (fractional repla cement rates of 0.87-3.14% per day). Naive-phenotype T cells were more abun dant, and the half-life of total T cells mas prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatie nt variation in T-cell kinetics may be reflective of differences in functio nal immune reconstitution after treatment for HIV-1 disease.