Shorter telomere length predicts poorer immunological recovery in virologically suppressed HIV-1-infected patients treated with combined antiretroviral therapy

Abstract

Background: Successful combined antiretroviral therapy (cART) does not always result in complete CD4 T-cell recovery despite the effective control of HIV replication. Because telomere dysregulation can lead to an abnormal cell proliferation, we hypothesized that the lack of CD4 recovery may be related to telomere defects; We thus evaluated the association between telomere length (TL) and CD4 T-cell recovery 48 weeks after cART initiation in virologically suppressed patients, and its possible relationship to oxidative stress (OS) and nitrosative stress (NOx) markers.

Methods: We studied HIV-infected patients on stable cART who achieved a viral load <50 copies per milliliter after 48 weeks of their first cART. Leukocyte TL was measured and categorized into tertiles. We calculated mean increases in CD4 T-cell at 48 weeks from cART initiation and used multivariate linear regression models to estimate differences in mean increases according to tertiles of TL.

Results: One hundred thirty-two patients, 86% male, 81% <50 years at cART initiation were studied. Mean increases in CD4 were greater in patients with long TL than in those with medium and short TLs (P = 0.007). After adjustment for sex, age, CD4 T-cell counts, viral load, and hepatitis C infection at cART initiation, differences in mean CD4 T-cell count increases according to TL remained statistically significant (P = 0.02). Additional adjustment for NOx and OS did not change the results.

Conclusion: A lower immunological response despite a successful virological response is associated with a shorter TL. The effect is not related to NOx or OS.