- Poster presentation
- Open Access
Mitochondrial effects of 3 years of CD4-guided HIV treatment interruption
© Garrabou et al; licensee BioMed Central Ltd. 2008
- Published: 10 November 2008
- Mitochondrial Function
- Viral Suppression
- Toxicity Mechanism
- Mitochondrial Content
- Mitochondrial Toxicity
Mitochondrial toxicity of antiretroviral treatment (ARVT), especially nucleoside-analogues' capacity to inhibit DNA-polymerase gamma, has been proposed as the ethiopathological mechanism which underlies many of the secondary effects of HIV therapy. The aim of the present study was to evaluate whether a prolonged CD4 cell-guided ARVT interruption could reverse mitochondrial toxicity.
We included 38 patients from the TIBET study whose peripheral blood mononuclear cells (PBMCs) had been collected at baseline, at 96 and at 144 weeks throughout the study period; 18 of them discontinued ARVT along this time and 20 maintained therapy. Mitochondrial DNA (mtDNA) content was measured by real-time PCR and mitochondrial function through the spectrophotometric measurement of cytochrome C oxidase (COX) enzymatic activity normalised by mitochondrial content using citrate synthase (CS) activity (COX/CS ratio).
Whereas mtDNA content showed a similar progressive decrease throughout the study period in both study arms, only for the control group was this significant either at week 96 (15% decrease, p = 0.03) or at week 144 (34% decrease, p = 0.01). The COX/CS ratio significantly improved in patients who interrupted antiretroviral therapy in comparison with those who did not, especially at week 96 (130% increase, p = 0.06). The univariate and multivariate analysis performed showed that only CD4+ T-cell value at the time of ARVT initiation and time with viral suppression before the study were associated with changes in the COX/CS ratio.
PBMCs' mitochondrial function improved during a prolonged ARVT interruption in spite of mtDNA content decrease. The absence of correlation between mitochondrial parameters suggests the existence of a mitochondrial transcriptional or translational upregulation mechanism which could be increasing mitochondrial protein expression in the absence of mtDNA content improvement, or also could be the reversion of an ARV-mediated mitochondrial toxicity mechanism that was previously disturbing mitochondrial function through a DNA polymerase gamma-independent way.
This study was supported by: Fundació la Marató de TV3 020210 and 020631, FIPSE 36612/06, FIS 40381/04 and 41239/04, Suports a Grups de Recerca de la Generalitat de Catalunya 2005/SGR/0300 and CIBER de Enfermedades Raras (initiative of the ISCIII).
This article is published under license to BioMed Central Ltd.