Determinants of blood telomere length in antiretroviral treatment‐naïve HIV‐positive participants enrolled in the NEAT 001/ANRS 143 clinical trial

Abstract

Objectives Our aim was to investigate factors associated with baseline blood telomere length in participants enrolled in NEAT 001/ANRS 143, a randomized, open‐label trial comparing ritonavir‐boosted darunavir (DRV/r) plus raltegravir (RAL) with DRV/r plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in antiretroviral therapy (ART)‐naïve HIV‐positive adults. Methods A cross‐sectional study of 201 randomly selected participants who had stored samples available was carried out. We measured telomere length (i.e. the relative telomere length, calculated as the telomere to single copy gene ratio) at baseline with monochrome quantitative multiplex polymerase chain reaction (PCR). We used multivariable predictive linear regression to calculate mean differences and 95% confidence intervals (CIs) for the association between baseline telomere length and baseline characteristics. Results The baseline characteristics of the 201 participants did not differ from those of the 805 participants in the parent trial population: 89% were male, the mean age was 39 years, 83.6% were Caucasian, 93% acquired HIV infection via sexual transmission, the mean estimated time since HIV diagnosis was 2.1 years, the mean HIV‐1 RNA load was 4.7 log10 HIV‐1 RNA copies/mL, the mean nadir and baseline CD4 counts were 301 and 324 cells/μL, respectively, and the mean CD4:CD8 ratio was 0.4. In the univariate analysis, shorter telomere length was associated with older age (per 10 years) (P < 0.001), HIV‐1 RNA ≥ 100 000 copies/mL (P = 0.001), CD4 count < 200 cells/μL (P = 0.037), lower CD4:CD8 ratio (P = 0.018), statin treatment (P = 0.004), and current alcohol consumption (P = 0.035). In the multivariable analysis, older age (P < 0.001) and HIV RNA ≥ 100 000 copies/mL (P = 0.054) were independently associated with shorter telomere length. Conclusions Both age and HIV RNA viral load correlated with shorter blood telomere length in untreated persons living with HIV. These results suggest that HIV infection and age have synergistic and independent impacts upon immunosenescence.

Ageing with HIV: Challenges and biomarkers

“…Compared to uninfected adults, PLWH have shorter leucocyte TL; which negatively correlates with viral load in untreated patients ( Table 2 ). 59 , 60 This TL attrition is pronounced and occurs rapidly after seroconversion, 61 , 62 Early introduction of ART partially recovers leucocyte TL because of the immune reconstitution process that shifts towards less differentiated cells with longer TL. 63 This positive effect of ART on TL, diminishes when ART initiation is delayed.…”

Decrypting biological hallmarks of aging in people with HIV

“…Telomere length shortening progressively occurs with aging and is linked to age-related diseases [36]. Recent findings demonstrate a higher extent of telomere length shortening observed in untreated HIV is associated with both age and viral load [37]. Although ART regimens, including those containing tenofovir, could impact telomere length by affecting telomerase activity [38], progressive telomere length shortening is associated with delaying ART initiation [39].…”

Association between Combination Antiretroviral Therapy and Telomere Length in People Living with Human Immunodeficiency Virus

“…Untreated HIV infection and ageing had a synergistic effect on telomere shortening. It was calculated that a viral load of >100,000 copies/mL of blood plasma affected telomere length similarly to 7 years of ageing and concluded that an HIV-infected person with a viral load >100,000 copies/mL compared to an HIV-negative person with the same chronological age could have the telomere length of a person almost two decades older [ 28 ]. Untreated HIV infection will progress.…”

“…To understand the progression of HIV infection, the number of CD4+ T cells is monitored [ 29 ]. The number of CD4+ T cells < 200 cells/µL was associated with shortened telomeres [ 28 ]. The parameter often used to track inflammation [ 30 ] and the progression of HIV infection [ 29 ] is C-reactive protein (CRP).…”