Purpose of the Study
To evaluate the kinetics of immune reconstitution after triple combination therapy for human immunodeficiency virus (HIV)-infected patients.
33 HIV-infected adults with CD4+ T lymphocyte counts ≥50 cells/μL, plasma HIV RNA level ≥30 000 copies/mL, and no previous antiretroviral treatment.
Subjects received triple antiretroviral therapy (ritonavir, zidovudine, lamivudine). Peripheral blood CD4, CD8, CD19, CD45RA, CD45RO, and CD62L cell analyses were performed at multiple time points over 36 weeks of treatment. Mathematical modeling for CD4+ and CD8+ T cell recovery was performed.
Both CD4+ and CD8+ T cell recovery during antiretroviral therapy showed a biphasic pattern. Rapid recovery occurred during the first 3 weeks for CD4+ T cells, and first 6 weeks for CD8+ T cells; most of them were “memory/effector” T cells (CD45RO+ or CD45RA+CD62L−). The early recovery of memory CD4+ and CD8+ T cells was followed by a slow recovery period of CD4+ and CD8+ T cells that were largely “naı̈ve” (CD45RA+CD62L+), with virtually no further recovery of memory T cells.
Based on mathematical modeling analyses, the initial rapid increase in memory CD4+ and CD8+ T cells after the triple antiviral therapy result from redistribution, but not T cell proliferation. A gradual repopulation of the T cell compartment then follows with newly produced naı̈ve T cells.
Ideally, the ultimate goal of HIV therapy is not only to stop viral replication and eradicate the virus, but also to restore immune function in the compromised host. In contrast to previous studies, this article provides a deeper understanding of the nature of T cell compartment reconstitution after triple antiretroviral therapy. Evidence that there is a gradual repopulation of the T cell compartment with newly generated naı̈ve T cells is indeed encouraging. An accompanying article by Gorachov (reviewed below), and a brief editorial entitled “Getting to the HAART of T cell dynamics” by Roederer in the same issue of Nature provide further relevant insights.