Telomere length (TL) and telomerase activity (TA) require further study as biomarkers of age-related disease among persons with HIV (PWH). We assessed factors associated with short TL and associations between TL, TA and age-related co-morbidities among PWH on suppressive ART.
A nested case-control study using clinical data and banked PBMCs from ACTG Longitudinal Linked Randomized Trials (ALLRT). Cases had: (1) sustained plasma HIV RNA (VL) suppression to <200 copies/mL within 24 weeks of ART initiation and for ≥96 weeks; (2) non-accidental death or confirmed diagnosis of cancer, cardiovascular, liver, renal, neurocognitive, or pulmonary disease, bone fractures or diabetes; (3) banked PBMC pre-ART, week 48 and pre-event. For each case, there were 2 controls matched for sex, age and duration of NRTI. TL was determined using qPCR with relative TL measured by quantifying a telomere repeat copy versus single copy reference gene ratio (T/S ratio). TA was determined using a real-time quantitative telomerase repeats amplification protocol (RQ-TRAP). TA data were log[sub]10[/sub] transformed. Univariable and multivariable conditional logistic regression evaluated associations between TL, TA and disease.
We studied 351 participants (117 cases, 234 controls); 23% female, 53% non-white, 8% IDU and 56% smokers. Pre-ART, median age was 42 years, CD4 cells/µl 253, CD8 cells/µl 766, CD4/CD8 ratio 0.25, VL 4.7 log10 copies/mL, TL 0.41 and TA 1.9 log10. Among incident cases, 14 (35%) were diabetes, 33 (28%) renal disease, 18 (15%) cancer, 14 (12%) CVD, 7 (6%) death and 4 (4%) bone fractures. Short pre-ART TL (<0.4 T/S ratio) was associated with pre-ART VL >105 copies/mL (OR=1.9; 95% CI 1.2-3.0) and pre-ART TA in the lowest quartile (OR 1.8; 95% CI 1.0-3.2). We found no associations between short pre-ART TL and age, smoking, CD4 or CD4/CD8 ratio. Factors positively associated with age-related disease were earlier calendar study entry year, pre-ART CD4<200 cells/µl, higher pre-ART VL, initial ART regimen without TDF, lower CD4/CD8 ratio at 96 weeks and smoking. Neither pre-ART TL nor TA were associated with age-related disease in univariable or multivariable analyses.
Pre-ART telomeres were significantly shorter among PWH with higher VL levels; however, pre-ART TL and TA were not associated with age-related disease. Longitudinal data of changes in TL and TA during ART and associations with disease events are forthcoming.