Abstract:
Children who are human immunodeficiency virus (HIV)-exposed but uninfected
(CHEU) accumulate maternal HIV and antiretroviral exposures through pregnancy, postnatal
prophylaxis, and breastfeeding. Here, we compared the dynamics of mitochondrial DNA (mtDNA)
parameters in African breastfed CHEU receiving lopinavir/ritonavir (LPV/r) or lamivudine (3TC)
pre-exposure prophylaxis during the first year of life. The number of mtDNA copies per cell (MCN)
and the proportion of deleted mtDNA (MDD) were assessed at day 7 and at week 50 post-delivery
(PrEP group). mtDNA depletion was defined as a 50% or more decrease from the initial value,
and mtDNA deletions was the detection of mtDNA molecules with large DNA fragment loss. We also
performed a sub-analysis with CHEU who did not receive a prophylactic treatment in South Africa
(control group). From day seven to week 50, MCN decreased with a median of 41.7% (interquartile
range, IQR: 12.1; 64.4) in the PrEP group. The proportion of children with mtDNA depletion was
not significantly different between the two prophylactic regimens. Poisson regressions showed that
LPV/r and 3TC were associated with mtDNA depletion (reference: control group; LPV/r: PR = 1.75
(CI95%: 1.15–2.68), p < 0.01; 3TC: PR = 1.54 (CI95%: 1.00–2.37), p = 0.05). Moreover, the proportion of
children with MDD was unexpectedly high before randomisation in both groups. Long-term health
impacts of these mitochondrial DNA parameters should be investigated further for both CHEU
and HIV-infected children receiving LPV/r- or 3TC- based regimens.
