Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor beta chain repertoire and reduces the level of T-cell oligoclonality

Major T-cell receptor beta chain variable region (TCRBV) repertoire perturb ations are temporally associated with the downregulation of viremia during primary human immunodeficiency virus (HIV) infection and with oligoclonal e xpansion and clonal exhaustion of HIV-specific cytotoxic T lymphocytes (CTL s). To determine whether initiation of antiretroviral therapy (ART) or high ly active antiretroviral therapy (HAART) during primary infection influence s the dynamics of T-cell-mediated immune responses, the TCRBV repertoire wa s analyzed by semiquantitative polymerase chain reaction in serial blood sa mples obtained from 11 untreated and 11 ART-treated patients. Repertoire va riations were evaluated longitudinally. Stabilization of the TCRBV repertoi re was more consistently observed in treated as compared with untreated pat ients. Furthermore, the extent and the rapidity of stabilization were signi ficantly different in treated versus untreated patients. TCRBV repertoire s tabilization was positively correlated with the slope of HIV viremia in the treated group, suggesting an association between repertoire stabilization and virologic response to treatment. To test whether stabilization was asso ciated with variations in the clonal complexity of T-cell populations, T-ce ll receptor (TCR) heteroduplex mobility shift assays (HMAs) were performed on sequential samples from 4 HAART-treated subjects. Densitometric analysis of HMA profiles showed a reduction in the number of TCR clonotypes in most TCRBV families and a significant decrease in the total number of clonotype s following 7 months of HAART. Furthermore, a biphasic decline in HIV-speci fic but not heterologous CTL clones was observed. This indicates that ART l eads to a global reduction of CD8(+) T-cell oligoclonality and significantl y modulates the mobilization of HIV-specific CTL during primary infection, (C) 2000 by The American Society of Hematology.