Partial Recovery of Telomere Length After Long-term Virologic Suppression in Persons With HIV-1

Abstract

Background: People with HIV-1 (PWH) age differently than the general population. Blood telomere length (BTL) attrition is a surrogate biomarker of immunosenescence and aging in PWH. BTL is reduced immediately after HIV-1 infection and recovers in PWH with long-term virologic suppression, but the extent of this recovery is unknown.

Methods: This prospective 6-year observational study assessed the evolution of BTL in PWH who were virologically suppressed. A cross-sectional analysis additionally compared BTL with age- and sex-matched blood donors and sex-matched persons older than 60 years from a general population cohort. DNA from whole blood was isolated, and relative BTL was determined by monochrome quantitative multiplex polymerase chain reaction assay and expressed as the ratio of telomere to single-copy gene (T/S).

Results: A total of 128 PWH were included in the prospective 6-year observational study. These same 128 PWH (median age, 55 years; 27.3% women) were compared cross-sectionally at 6-year follow-up with 128 age- and gender-matched blood donors (median age, 55 years) and 128 gender-matched individuals older than 60 years from a general population cohort (median age, 70 years). An inverse correlation between age and BTL was observed. The median BTL of PWH was shorter than their matched blood donors (T/S, 1.07 [IQR, 0.95-1.17] vs 1.28 [IQR, 1.12-1.48]; P < .001) but longer than the elderly population (T/S, 0.89 [IQR, 0.77-0.98], P < .001). PWH experienced a BTL increase at 6 years of 2.9% (T/S, 1.04 vs 1.07; P = .002). In PWH, age was associated with a shorter BTL (coefficient, -0.007 45, SE = 0.002 04, P = .002) and baseline lower CD4 count with a gain in BTL (coefficient, -0.000 06, SE = 0.000 02, P = .004). Shorter baseline BTL (odds ratio, 0.91 [95% CI, .87-.94]; P < .001) and higher glucose levels (odds ratio, 1.04 [95% CI, 1.02-1.07]; P = .003) were associated with a greater similarity of BTL to the elderly population.

Conclusions: PWH with long-term virologic suppression experience a trend toward an increased BTL after 6 years of follow-up. Middle-aged people with long-term controlled HIV-1 have a shorter BTL than expected for their chronologic age but longer than that of people 15 years older in the general population.

Keywords: HIV; aging; immune reconstitution; telomere.

Figure 1.

Differences in blood telomere length (BTL) among the groups. A, This lollipop diagram shows an individual BTL, measured as the ratio of telomere to single-copy gene (T/S), for each participant in ascending order: persons with HIV-1 (PWH) after a 6-year follow-up (pink dots), age/sex-matched blood donors (green dots), and the general population aged >60 years (orange dots). B, This violin plot compares the BTL in the 3 groups of participants. Dots represent individual data: PWH at baseline (blue) and after a 6-year follow-up (pink), age/sex-matched blood donors (dots), and the general population aged >60 years (orange). Red dots show the medians and box plots show IQRs. The width of each curve corresponds to the approximate frequency of data points for a given BTL.

Figure 2.

Correlation between age and blood telomere length in people with HIV-1 (PWH) and blood donors at 6 years of follow-up. Dots show individual data, and lines show correlation curves of PWH (red) and their age- and sex-matched blood donors (green). Shaded areas represent the 95% CI.