In this study, changes in plasma virus load, peripheral blood CD4 T cell counts and the T cell repertoire were assessed in eight chronically HIV-infected individuals suspending antiretroviral therapy. Despite rapid increases in virus load and substantial CD4 T cell losses during treatment interruption, no marked changes in the T cell receptor β chain repertoire were observed. The magnitude of associated T cell repertoire perturbation thus contrasts with that observed during primary HIV infection.

During primary HIV infection, the activation and expansion of HIV-specific T cells globally affects the T cell receptor (TCR) repertoire at the level of relative representation of individual TCRβ variable (V) chain gene families [1, 2]. The extent of TCR repertoire perturbation signifies the strength of the anti-HIV T cell response; however, moderate perturbations within multiple TCRβV gene families predict a more benign subsequent disease course than do severe perturbations within fewer TCRβV families [2]. This general association suggests that a more diverse anti-HIV T cell response provides for a more effective and lasting immune suppression of HIV replication. The residual significance of this relationship between the immune response and disease course, now that effective suppression of HIV replication is often mediated by highly active antiretroviral therapy, is largely unknown. In this study, our objectives were to determine whether TCR repertoire perturbations were detectable at the level of relative TCRβV gene family representation during treatment interruption, and if so, whether, as in primary HIV infection, the pattern of TCR repertoire perturbation relates to the nature of the subsequent changes in virus load or CD4 T cell counts.