Researchers, led by Javier Rodríguez-Centeno, PhD, from the Institute for Health Research Hospital La Paz (IdiPAZ) in Madrid, Spain, examined whether the negative impact of the antiviral tenofovir on telomere length (TL) was attributable to immune reconstitution interference or the inhibition of telomerase. The study, published in the Journal of Antimicrobial Chemotherapy, concluded that in patients with long-term human immunodeficiency virus (HIV) infections, the inhibition of telomerase from tenofovir therapy could be the driver of telomere shortening in CD8+ T cells.
The trial included 128 patients with long-term HIV who were treated with regimens that did (n = 79) or did not contain (n = 49) tenofovir. The primary parameters used in comparing the groups were TL in whole blood, peripheral blood mononuclear cells (PMBCs), CD4+ T cells, and CD8+ T cells, as well as telomerase activity and T cell maturational subset distribution.
The analysis showed that participants treated with regiments containing tenofovir for at least four years had shorter TL in CD8+ T cells (p = 0.04), and lower telomerase activity in CD4+ (p = 0.012) and CD8+ T cells (p = 0.023). The researchers also noted that tenofovir treatment was associated with lower proportions of RTE CD4+ cells (p = 0.031) and PD1 marker expression (p = 0.013).
The authors also reported that there was no shortening in the CD4+ compartment, and they theorized that the “decrease in telomerase activity could be explained both by the inhibition by tenofovir and by the lower proportion of recent thymic emigrant (RTE)] CD4+ cells.”
The researchers elucidated the association of telomerase shortening and reduced activity with tenofovir treatment in patients with long-term HIV infections and posited that the negative effects were mediated by telomerase, inhibition rather than inhibition of the immune reconstitution interface.
Source: Journal of Antimicrobial Chemotherapy
