Purpose of the Study
To study the diversity of the T lymphocyte repertoire during the course of human immunodeficiency virus (HIV)-1 infection and after combination antiretroviral therapy.
Eleven HIV-infected adults undergoing triple antiviral therapy were compared with 7 untreated HIV-infected adults and 5 noninfected controls.
Assessment of T-cell antigen receptor (TCR) repertoire in CD4+ and CD8+ T cells by TCR sequence analysis.
In nontreated HIV-infected subjects, CD8+ T cell TCR repertoire showed drastic alteration at all stages that were independent of clinical status, CD4+ or CD8+ T cell counts, or viral load. The severity of alteration of the CD4+ T cell repertoire was associated with viremia or CD4+ cell counts: patients with high CD4+ cell counts and low viremia had normal CD4+ T cell repertoire diversity; in contrast, higher viremia or lower CD4+ cell counts in patients with progressive disease were associated with reduction in CD4+ repertoire diversity. In patients with successful triple therapy, after 3 to 6 months of the treatment, CD4+ T cell repertoire normalized to match seronegative controls.
CD4+ T cell TCR repertoire is restored within the first 6 months of successful triple therapy, in contrast to persistent restriction of CD8+ TCR repertoire.
One important measure of the integrity of the T lymphocyte arm of the immune system is to determine TCR repertoire diversity, which provides insight to the variety of antigens that T cells can recognize. The encouraging finding of this study is that the restricted CD4+ TCR repertoire in HIV-infected patients can be normalized after the triple antiretroviral therapy. The normalized T cell repertoires, combined with results of Pakker's study showing increased naı̈ve T cells after 4 to 6 months of treatment, suggest that the CD4+ T cell compartment of successfully treated HIV patients might be restored in quality as well as quantity (ie, CD4+ T cell counts) with triple therapy. A brief editorial entitled “Getting to the HAART of T cell dynamics” by Roederer on pages 145 to 146 of the same issue ofNature is an insightful summary of these articles.