Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1

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.

Mitochondrial DNA Profiling in A Cohort of Antiretroviral Treated HIV Patients in Lagos, Nigeria: Assessment of Long-Term Effects of cART on Life Quality of PLWH

“…Likewise, [43] found no such variation between ART-treated patients (age < 50 years with suppressed viral load) and healthy controls. All these studies aimed at identifying the level of depletion of mtDNA concentration in functional cells such as PBMC which were expected to be lower due to mitochondrial dysfunction induced by disease condition and exposure to cART, as compared to healthy controls [40]- [43]. However, studies targeting DAMPenhanced plasma mtDNA (known as cf-mtDNA) concentration as the case in this study, would hypothesize elevated mtDNA concentration among ART-treated HIV patients due to possible high oxidative damage and impairment in mitochondrial function, supposedly enhanced Reference [21] reported a higher cf-mtDNA concentration among ART-treated compared to ART-naive HIV patients, but the study did not include healthy controls.…”

“…However, [33] did not find significant variation of cf-mtDNA level between ART-treated patients and healthy control. There have been studies that investigated mtDNA concentration in peripheral mononuclear cells or whole blood of PLWH who were on cART treatment or in children who received ART as prophylactics in Africa [34]- [40], but little or no report has been documented on cf-mtDNA in HIV patients from any part of Africa regions.…”

Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis

“…Among PROMISE M&S participants, we randomly selected 198 CHEU with 1:1 sex and prophylactic regimen ratios. The same selection criteria were used in a previous study investigating the mitochondrial DNA genotoxicity of the prophylaxis [ 38 , 39 ].…”

“…Second, we investigated the association between telomere length and shortening with mitochondrial DNA content using linear regression in an analysis restricted to CHEU from Burkina Faso and Uganda ( n = 73). Zambia was excluded from the analyses because we previously reported an interaction between mitochondrial DNA content and platelet count [ 38 , 39 ]. Mitochondrial DNA depletion was defined as a 50% or more decrease in mitochondrial DNA copy number per cell from day-7 to week-50 [ 38 ].…”

“…Zambia was excluded from the analyses because we previously reported an interaction between mitochondrial DNA content and platelet count [ 38 , 39 ]. Mitochondrial DNA depletion was defined as a 50% or more decrease in mitochondrial DNA copy number per cell from day-7 to week-50 [ 38 ]. Mitochondrial DNA content at day-7, week-50, and year-6 were incremented per 50 copies.…”