title: Evolution of mitochondrial DNA content after planned interruption of HAART in HIV-infected pediatric patients.
abstract: HAART-related long-term toxicities, many of them ascribed to mitochondrial (mt) toxicity of the nucleoside analogues, are being increasingly reported in HIV-infected children. HIV infection can also cause mt damage. Case series include 13 vertically HIV-infected pediatric patients (9 girls, median age 10.5 years) with optimal long-term response to a first-line HAART regimen who underwent planned treatment interruption (PTI). MtDNA content from peripheral blood mononuclear cells was assessed by means of a real-time PCR technique at PTI and 12 months later and expressed as an mtDNA/nuclear DNA ratio, together with lactate levels. At PTI, patients had remained a median time of 4.7 years on HAART and 4.3 years with complete suppression of viral replication. The main reason leading to PTI was treatment fatigue. One month after PTI, HIV plasmatic viral load had increased to 4.8 log copies/ml and stabilized thereafter. During the 12-month study period, all children remained free from any HIV-related clinical event. A progressive and significant decrease in median CD4 cell counts and percentages was observed 12 months after PTI. One year after PTI, the median mtDNA/nuclear DNA ratios had increased from 0.76 to 1.08 (p = 0.002) and lactate levels had decreased (from 1.12 to 0.73 mmol/liter; p = 0.019). Changes in mtDNA did not correlate with changes in lactate levels. No relationship was found between the evolution in mt toxicity markers and the rest of the clinical, immunological, and virological variables. In this series, PTI led to a partial restoration of mtDNA levels and a significant decrease in lactate values.
authors: Unitat d'Infectologia, Servei de Pediatria, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain. ton@hsjdbcn.org
authors: Antoni
authors: A
authors: Noguera
authors: Constanza
authors: C
authors: Morén
authors: Núria
authors: N
authors: Rovira
authors: Emília
authors: E
authors: Sànchez
authors: Glòria
authors: G
authors: Garrabou
authors: Mireia
authors: M
authors: Nicolàs
authors: Carmen
authors: C
authors: Muñoz-Almagro
authors: Francesc
authors: F
authors: Cardellach
authors: Oscar
authors: O
authors: Miró
authors: Clàudia
authors: C
authors: Fortuny
mesh_terms: D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000187:drug effects*; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D028761:Withholding Treatment
chemical_list: D004272:DNA, Mitochondrial