Aging in HIV/AIDS: Hélène Côté makes breakthroughs in understanding the risks of HIV therapies

Approximately 3 million HIV-infected women become pregnant every year and approximately 90% of HIV-infected children acquire HIV through mother-to-child transmission. To prevent transmission and/or for their own health, HIV-infected women can receive highly active antiretroviral therapy (HAART) during pregnancy. This greatly decreases the risk of mother-to-child transmission, from 20-25% to <2%.

Although the benefits of HAART in pregnancy clearly outweigh the risks, the consequences of taking ircuthese drugs over the long term is poorly understood. It is known, however, that nucleo(s/t)ide reverse transcriptase inhibitor (NRTI)-containing HAART can interfere with mitochondrial DNA (mtDNA) integrity, leading to mitochondrial dysfunction and oxidative stress. Since NRTIs can cross the placenta, these may affect mtDNA in developing foetuses. Indeed, given the high rates of mtDNA replication during embryogenesis and organogenesis, the unborn child could be at increased risk for mtDNA damage.

To assess the effects of HAART, Marissa H.J. Jitratkosol and collaborators, working in a lab under the supervision of CBR member Dr. Hélène Côté, investigated the incidence of random mtDNA point mutations in HIV-uninfected children and their mothers who were either HIV-infected HAART-treated in pregnancy or HIV-negative.

Marissa Jitratkosol and Hélène Côté

As reported in the journal AIDS, they found that there was no significant difference between the percentage of HIV/HAART-exposed infants with AC/TG mutations (N=15/57, 26.3%) and controls (N=10/70, 14.3%) before (p=0.090) or after. However, significantly more HIV/HAART-exposed mothers (N=18/42, 42.9%) harboured AC/TG mutations compared to controls (N=7/39, 17.9%) before (p=0.015) and after (p=0.012).  AC/TG mutations were more common in HIV/HAART-exposed mothers than in their infants (N=42, 42.9% vs. 23.8% p=0.033), however, this difference disappeared after controlling for confounders. No difference was seen between control mothers and their infants (N=39, both 17.9%). In HIV/HAART-exposed mothers, only a detectable HIV plasma viral load near delivery predicted AC/TG mutations.

These important results suggest that HIV and/or HAART exposure is associated with increased prevalence of AC/TG mtDNA mutations in mothers and show a similar tendency in infants exposed during pregnancy. Since accumulation of mtDNA mutations has been linked with aging and age-associated diseases, these novel findings highlight concerns in the long term for HIV and HAART-exposed populations and are rationale for continued development of new, safer therapies.

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