Effects of tenofovir on telomeres, telomerase and T cell maturational subset distribution in long-term aviraemic HIV-infected adults

Objectives To evaluate whether the negative impact of tenofovir on telomere length (TL) is due to immune reconstitution interference or inhibition of telomerase. Methods One hundred and twenty-eight long-term aviraemic HIV adults treated with tenofovir-containing (n = 79) or tenofovir-sparing regimens (n = 49) were recruited to compare the following: TL in whole blood, PBMCs, CD4+ T cells and CD8+ T cells by quantitative PCR (qPCR); telomerase activity in PBMCs, CD4+ cells and CD8+ T cells using the TRAPeze RT Telomerase Detection Kit; and T cell maturational subset distribution by flow cytometry. Results In an adjusted analysis, participants treated with tenofovir for at least 4 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). Tenofovir treatment was also associated with lower proportions of recent thymic emigrant (RTE) CD4+ cells (P = 0.031) and PD1 marker expression (P = 0.013). Conclusions In long-term aviraemic HIV adults, the inhibition of telomerase by tenofovir could explain telomere shortening in CD8+ T cells. There is no telomere shortening in the CD4+ compartment and the decrease in telomerase activity could be explained both by the inhibition by tenofovir and by the lower proportion of RTE CD4+cells.

Automated summary

This study found that in long-term aviraemic HIV adults, tenofovir can cause telomere shortening in CD8+ T cells by inhibiting telomerase activity, but does not cause telomere shortening in CD4+ T cells. Tenofovir treatment may also lead to a decrease in the proportion of RTE CD4+ cells and a decrease in PD1 marker expression.