Leukocyte Telomere Length in HIV-Infected and HIV-Exposed Uninfected Children: Shorter Telomeres with Uncontrolled HIV Viremia

Abstract

Objectives Nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV antiretroviral therapy can inhibit human telomerase reverse transcriptase. We therefore investigated whether in utero or childhood exposure to NRTIs affects leukocyte telomere length (LTL), a marker of cellular aging. Methods In this cross-sectional CARMA cohort study, we investigated factors associated with LTL in HIV -1-infected (HIV + ) children (n = 94), HIV-1-exposed uninfected (HEU) children who were exposed to antiretroviral therapy (ART) perinatally (n = 177), and HIV-unexposed uninfected (HIV − ) control children (n = 104) aged 0–19 years. Univariate followed by multivariate linear regression models were used to examine relationships of explanatory variables with LTL for: a) all subjects, b) HIV + /HEU children only, and c) HIV + children only. Results After adjusting for age and gender, there was no difference in LTL between the 3 groups, when considering children of all ages together. In multivariate models, older age and male gender were associated with shorter LTL. For the HIV + group alone, having a detectable HIV viral load was also strongly associated with shorter LTL (p = 0.007). Conclusions In this large study, group rates of LTL attrition were similar for HIV + , HEU and HIV − children. No associations between children’s LTL and their perinatal ART exposure or HIV status were seen in linear regression models. However, the association between having a detectable HIV viral load and shorter LTL suggests that uncontrolled HIV viremia rather than duration of ART exposure may be associated with acceleration of blood telomere attrition.

Abnormal Bone Acquisition With Early-Life HIV Infection: Role of Immune Activation and Senescent Osteogenic Precursors

“…Relative average telomere lengths in COP cells (LIN−/OCN+) were measured using qPCR with methodology modified from Cote and colleagues, (27) Cawthon and colleagues, (28) Shaffer and colleagues, (29) and Honig and colleagues, (30) and expressed as the ratio of telomere (T) and a single copy nuclear gene coding for the accessory subunit of polymerase gamma (ASPG or POLG2) which was used for nuclear DNA (S) copy number on the plate with DNA standards. The assay coefficients of variation (CVs) were 5% and 8%, respectively.…”

Premature B-cell senescence as a consequence of chronic immune activation

“…50 Moreover, shorter lymphocyte telomere length was reported for viremic HIV-1 infected children as compared with healthy controls. 52 Interestingly, increased frequencies of both DN and MA were also observed in the blood of kidney transplant pediatric patients. 53 In view of this, it is interesting to consider HIV-1 infected and kidney transplant patients as different models of secondary immune deficiency characterized by chronic immune activation.…”

Rapid Decrease in Peripheral Blood Mononucleated Cell Telomere Length After HIV Seroconversion, but Not HCV Seroconversion

“…7,8 In fact, exposure to combination antiretroviral therapy has been associated with longer telomere length in individuals living with HIV. 9,10 …”