The HIV-negative infants of HIV-positive mothers who took antiretroviral therapy to prevent vertical transmission of HIV, have a small risk of mitochondrial dysfunction according to French researchers.
Investigators conducted a systematic analysis of unexplained symptoms consistent with mitochondrial dysfunction in the EPF French cohort of children born to HIV-positive mothers. Only HIV-negative children who had received follow-up for at least 18 months were included in this study, which is published in the August 15th edition of AIDS and comes only a month after presentations to the IAS conference in Paris suggested that infants born to HIV-positive mothers who took antiretrovirals to prevent transmission of HIV do not have a significantly increased risk of mitochondrial damage.
In a prospective study, the medical records of over 4,000 HIV-negative children up to 18 months were examined for unexplained symptoms consistent with mitochondrial damage. The investigators then examined each case with the child’s doctor to reach a consensus about the probable cause of mitochondrial dysfunction.
Tissue samples, MRI scans and lactic acid levels were checked in children when it was concluded that mitochondrial damage was caused by, or probably attributable to, the mother’s HIV status or antiretroviral drug use.
Of 4426 HIV-negative children included in the study, 29 had symptoms of mitochondrial toxicity with no apparent cause other than their mother’s health status. Seven of these children had established mitochondrial damage, 14 had possible damage, and investigations are proceeding for the remaining eight children. The incident rate for mitochondrial dysfunction in the HIV-negative children of HIV-positive mothers was 0.26, significantly higher than the 0.01 prevalence of mitochondrial disease seen in the general French infant population.
Abnormal lactic acid levels were detected in 11 of the 14 children with possible mitochondrial dysfunction, all but two of the children had abnormal cerebral MRI scans, and all but one child had histological findings indicative of mitochondrial dysfunction.
All the children with established or possible mitochondrial damage had been exposed to antiretroviral drugs. Furthermore, the risk associated with exposure to a combination of nucleoside analogues was significantly greater than that seen when a mother received AZT monotherapy (RR 2.5, 95% CI 1 – 1.65, p=0.0046).
The investigators conclude that perinatal exposure to nucleoside analogues is associated with “persistent mitochondrial disease.”
At last month's International AIDS Society conference in Paris, researchers from Cote d'Ivoire reported that of 140 infants exposed to ARVs in the Ditrame Plus study, 45% had at least one lactate measurement above 2.5mmol/L, and 14.8% had two measurements above 2.5mmol/L, with the mean peak of 3.3mmol/L. Objective clinical symptoms of hyperlactatemia such as weight loss were not observed, and hyperlactatemia resolved spontaneously in all but three cases. This study did not look at mitochondrial toxicity.
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Mother-to-baby transmission - factsheet
Barret B et al. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort. AIDS 17: 1769 – 1785, 2003.