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

Journal of Clinical Medicine

Nicolas Meda¹  Thorkild Tylleskär²  Chipepo Kankasa³  JamesK. Tumwine⁴  Pascal Reynier⁵  Mandisa Singata-Madliki⁶  Nobubelo Ngandu⁷  Ameena Goga⁷  PhilippeVan de Perre⁸  Nicolas Nagot⁸  Marianne Periès⁹  Roselyne Vallo⁹  Jean-Pierre Molès⁹  Audrey Monnin⁹ 

[1] Centre MURAZ, Bobo-Dioulasso 01 B.P. 390, Burkina Faso;Centre for International Health, Faculty of Medicine, University of Bergen, 5009 Bergen, Norway;Department of Paediatric and Child Health, University Teaching Hospital, Lusaka PO Box 50110, Zambia;Department of Paediatrics and Child Health, School of Medicine, College of Health Sciences, Makerere University, Kampala 7062, Uganda;Département de Biochimie et Génétique, Centre Hospitalier Universitaire, 49933 Angers, France;Effective Care Research Unit, Cecilia Makiwane Hospital, University of Fort Hare, East London 5201, South Africa;Health Systems Research Unit, South African Medical Research Council, Cape Town 7501, South Africa;Pathogenèse et Contrôle des Infections Chroniques, INSERM U1058, Université Montpellier, Centre Hospitalier Universitaire, 34934 Montpellier, France;Pathogenèse et Contrôle des Infections Chroniques, INSERM U1058, Université Montpellier, Etablissement Français du Sang, 34934 Montpellier, France;

关键词: mitochondrial DNA;    depletion;    deletion;    HIV-exposed uninfected children;    lopinavir/ritonavir;    lamivudine;   

DOI  :  10.3390/jcm9092972

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown