Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis.

Audrey Monnin,Philippe Van De Perre,Nicolas Meda,Sabrina Eymard-Duvernay,Chipepo Kankasa,Jean-Pierre Molès,Thorkild Tylleskär,Ameena Goga,Nicolas Nagot,Grace Ndeezi,Mandisa Singata-Madliki,James Kashugyera Tumwine,Amélie Vizeneux

doi:10.3390/children8090796

Abstract

Telomere shortening can be enhanced upon human immunodeficiency virus (HIV) infection and by antiretroviral (ARV) exposures. The aim of this study was to evaluate the acute and long-term effect on telomere shortening of two ARV prophylaxes, lopinavir/ritonavir (LPV/r) and lamivudine (3TC), administered to children who are HIV-exposed uninfected (CHEU) to prevent HIV acquisition through breastfeeding during the first year of life, and to investigate the relationship between telomere shortening and health outcomes at six years of age. We included 198 CHEU and measured telomere length at seven days of life, at week-50 and at six years (year-6) using quantitative polymerase chain reaction. At week-50, telomere shortening was observed among 44.3% of CHEU, irrespective of the prophylactic treatment. Furthermore, this telomere shortening was neither associated with poor growth indicators nor neuropsychological outcomes at year-6, except for motor abilities (MABC test n = 127, β = −3.61, 95%CI: −7.08, −0.14; p = 0.04). Safety data on telomere shortening for infant HIV prophylaxis are scarce. Its association with reduced motor abilities deserves further attention among CHEU but also HIV-infected children receiving ARV treatment.

Highlights

This article is an open access articleAssaying the short- and long-term safety of antiretroviral (ARV) therapy is of utmost priority for public health guidelines on ARV regimens for human immunodeficiency virus (HIV) prevention and treatment.Given the urgent need to prevent and treat HIV, most ARV regimens have been established by a panel of experts using evidence from randomized, phase 3 clinical trials that have directly compared ARV regimens in research settings
Telomere length did not significantly decrease until the six-year benchmark. Those identified with telomere shortening at week-50 did not demonstrate impaired growth or poorer clinical outcomes at year-6, but were associated with motor impairment
Given the absence of a control group not receiving any prophylactic treatment in this study, these observations suggest that both of the study drugs could have the same effect on telomere length, or that the telomere attrition we report is physiological

Summary

Introduction

This article is an open access articleAssaying the short- and long-term safety of antiretroviral (ARV) therapy is of utmost priority for public health guidelines on ARV regimens for HIV prevention and treatment.Given the urgent need to prevent and treat HIV, most ARV regimens have been established by a panel of experts using evidence from randomized, phase 3 clinical trials that have directly compared ARV regimens in research settings. Assaying the short- and long-term safety of antiretroviral (ARV) therapy is of utmost priority for public health guidelines on ARV regimens for HIV prevention and treatment. Many factors are associated with accelerated telomere shortening, such as male gender, smoking, alcohol consumption, ethnicity, obesity, sedentary lifestyle, genetic variants, socioeconomic status, as well as psychological stress [6,8]. Both ARV and HIV are known to promote telomere shortening. Chronic HIV-induced inflammation and free HIV viral particles themselves can enhance the production of reactive oxygen species damaging telomeric DNA and promoting telomere shortening [9,10,11]. A recent study reported a relationship between leucocyte telomere shortening and blood mitochondrial DNA content among HIV-infected or uninfected women, the greater the telomere shortening, the higher the mitochondrial DNA content [21]

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