People with HIV (PWH) are at high risk of aging-related diseases even while receiving antiretroviral therapy (ART). This premature aging might be reflected by biological aging biomarkers, one of which is telomere length, which is maintained by telomerase, a reverse transcriptase (RT) that can be inhibited in vitro by RT inhibitors, such as tenofovir (TFV). We investigated the impact of TFV on telomere length change in PWH over more than a decade.
121 PWH were taking ART and were assessed between 2003 and 2007 with comprehensive assessments and then re-assessed after a median 12.4 years in the CHARTER project. The most commonly used ART drugs at the second visit were emtricitabine (FTC, 65.3%), TFV alafenamide (TAF, 38.8%), dolutegravir (35.5%), lamivudine (25.6%), abacavir (24.8%), and darunavir (20.7%). Telomere length was measured in blood-derived cells by qPCR and was analyzed as the telomere to beta-globin single copy gene (T/S) ratio by mixed effects models that adjusted for demographic and disease characteristics as well as leukocyte count and duration of follow-up.
At the second visit, median age was 56 years, 11.7% were women, 43.3% were black, 94.0% had HIV RNA in plasma ? 200 cp/mL, and median CD4+ T-cells were 583/µL (current) and 64/µL (nadir). Median T/S ratio was 0.96 (IQR 0.84, 1.08) at the first visit and declined at the second visit (median -0.082, IQR (-0.02)-(-0.19), p<10-16). The T/S ratio of PWH who used TFV, either disoproxil fumarate (TDF, n=111 of 242 visits [45.9%]) or TAF (n=47 at the second visit only), declined more over time than of those who did not use tenofovir (p=0.049). Additional analysis identified that TAF (p=0.0022) but not TDF (p=0.72) was associated with greater T/S ratio decline (see Figure), even after multivariable adjustment (p=0.035). The only other ART drug that was associated with T/S ratio change was FTC (p=0.038) but the p value weakened (p=0.44) after adjusting for TAF use. Adjusting for use of FTC or other ART drugs did not weaken the relationship between TAF and T/S ratio.
PWH who use TAF have greater decline in telomere length than PWH who do not use TAF, even after accounting for demographic and disease characteristics. The inconsistent findings between TAF and TDF may be because intracellular TFV concentrations are higher with TAF than with TDF. A limitation is that TAF was not used at the first visit since it was not yet approved for clinical use so the findings should be confirmed in controlled trials.