MPV17-related mitochondrial DNA depletion syndrome is a rare, lethal, autosomal recessive primary mitochondrial disorder characterised by infantile onset liver disease and neurological features, including hypotonia, developmental delay, failure to thrive and neuropathy. The aim of this study was to describe the presentation and clinical course of infants diagnosed with MPV17 neurohepatopathy, comparing those who were HIV-exposed on antiretroviral therapy (ART), including zidovudine and nevirapine to prevent perinatal HIV transmission, to infants who were not HIV exposed, using data from a multicentre MPV17 natural history study in South Africa. Between 2013 and 2024, 25 infants were diagnosed with MPV17 neurohepatopathy, 8 (32%) of whom were HIV-exposed and received ART at birth (7 received zidovudine), none were HIV-infected. Median birth weight was lower at 2.45 kg (IQR 2.28–2.71) in infants who were HIV-exposed compared to 2.86 kg (IQR 2.54–3.13) in HIV-unexposed infants (p = 0.02). Symptom onset occurred much earlier at a median of 3 days of age (IQR 0–10 days) in HIV-exposed infants compared to 60 days (IQR 14–90) in HIV-unexposed (p = 0.006). Infants exposed to HIV were more likely to develop liver failure (p = 0.02). Perinatal therapy with the nucleoside reverse transcriptase inhibitor zidovudine, a known mitochondrial toxin, was associated with accelerated clinical presentation and clinical course of MPV17 neurohepatopathy. Our findings suggest that less toxic antiretroviral therapy should be considered for perinatal HIV prophylaxis in HIV-exposed infants, particularly in our setting where there is a high carrier frequency of a single pathogenic MPV17 variant.
Rose et al. (Tue,) studied this question.