Perinatal Exposure to Antiretroviral Therapy Is Associated with Increased Blood Mitochondrial DNA Levels and Decreased Mitochondrial Gene Expression in Infants

Abstract

When control infants and ART-exposed infants were compared, the mtDNA level was increased but mitochondrial gene expression was decreased in ART-exposed infants. These differences persisted after zidovudine was discontinued, suggesting that changes in mitochondrial proliferation and/or expression take place during and after ART exposure. These changes are likely the effects of the antiretroviral drugs on mitochondria. The clinical relevance and long-term impact of these alterations must be studied.

Research into a functional cure for HIV in neonates: the need for ethical foresight

“…These risks include mitochondrial toxic effects, transient growth and haematological ab normalities, anaemia, and changes in liver function. 21–24 The risk of mitochondrial toxic effects seems low 21,22 and it is not clear what their long-term significance is, or the extent to which they might be affected by HIV infection itself. 22 Investigators should carefully consider available evidence about the safety of specific drugs in neonates when selecting a combination ART regimen.…”

“…21–24 The risk of mitochondrial toxic effects seems low 21,22 and it is not clear what their long-term significance is, or the extent to which they might be affected by HIV infection itself. 22 Investigators should carefully consider available evidence about the safety of specific drugs in neonates when selecting a combination ART regimen. To reduce the risk of exposure of uninfected infants to ART, as previously discussed, mothers at high risk of transmission should be enrolled, and uninfected infants should be taken off ART as soon as possible.…”

Prevención de la transmisión vertical y efectos secundarios de la terapia anti-retroviral en hijos nacidos de madres seropositivas para VIH en el área Sur-Oriente de Santiago, Chile: perspectiva de 15 años

“…El diagnóstico de certeza de toxicidad mitocondrial se hace mediante la cuantificación del ADNmt o al menos un examen histológico en búsqueda de alteraciones ultra estructurales de la mitocondria y acúmulo de vacuolas grasas; actualmente sólo es posible efectuar niveles sanguíneos frente a la sospecha clínica. Durante los últimos años, se han realizado nuevos estudios que intentan identificar marcadores de toxicidad mitocondrial desde sangre materna, de cordón y de sangre periférica de recién nacido, entre los cuales se han medido niveles de ARN y ADN mitocondrial, apoptosis, síntesis de proteína mitocondrial materna y fetal, entre otros, pero con resultados disímiles 39,40 . De acuerdo a nuestros hallazgos y considerando el momento de presentación de las anormalidades de laboratorio, nos parece recomendable efectuar un seguimiento de los recién nacidos hijos de madre con infección por VIH expuestos a TARV que contemple: evaluación clínica y exámenes de laboratorio (hemograma, recuento de plaquetas, lactato plasmático, electrolitos plasmáticos,…”

Antiretroviral medications during pregnancy for therapy or prophylaxis

“…Côté et al [31] studied uninfected infants exposed to antiretrovirals in utero and a control group of infants not exposed to antiretrovirals or HIV. They demonstrated increased blood mitochondrial DNA levels but persistently decreased mitochondrial gene expression in the antiretroviral-exposed infants.…”