Mitochondrial DNA mutations in HIV-exposed uninfected infants following the cessation of triple antiretroviral drugs.

Abstract

Mitochondrial mutations in HIV-exposed uninfected (HEU) infants after cessation of ART are rarely studied. We analysed a group of HEU newborns born to mothers with late HIV diagnosis who received three doses of ART immediately after birth. We observed mitochondrial DNA (mtDNA) mutations at different times of withdrawal. The study was based on a clinical trial conducted from 2015 to 2020. Newborns of the intervention group who met the criteria for this study received triple antiretroviral drugs, zidovudine + lamivudine + nevirapine, within 2 h after the birth, as post-partum prophylaxis, and at 14 days were switched to zidovudine + lamivudine + lopinavir/ritonavir, which was continued until 6 weeks of age. From August to November 2019, blood samples from HEU infants were also collected after ceasing 12 months of ART, and analysed for mtDNA. Our study found that mtDNA mutations remained prevalent in HEU infants a few years after three ARTs were stopped immediately after birth. Among them, D-loop, ND1 and CYTB are the first three mutated regions during different withdrawal periods. This pattern of mutations is similar to, but not exactly consistent with, HIV-infected children receiving standard ART. Further studies are needed to determine the effects of these mutations on the development of HEU infants and whether stopping ART leads to the restoration of mitochondrial function.