Mitochondrial DNA and RNA increase in peripheral blood mononuclear cells from HIV-1-infected patients randomized to receive stavudine-containing or stavudine-sparing combination therapy.
BACKGROUND
Mitochondrial DNA (mtDNA) in peripheral blood mononuclear cells (PBMCs) has been suggested as a potential marker of mitochondrial toxicity associated with nucleoside analogue reverse-transcriptase inhibitor-containing therapy.


METHODS
We quantified mtDNA and mitochondrial RNA (mtRNA) in PBMCs over the course of 48 weeks in 78 patients infected with human immunodeficiency virus type 1 (HIV-1) who were randomly assigned to receive ritonavir-boosted indinavir and efavirenz with or without stavudine. Furthermore, we analyzed the association of mtDNA and mtRNA with clinical signs and symptoms and/or abnormalities in laboratory markers attributed to mitochondrial toxicity.


RESULTS
No statistically significant difference was found in mtDNA and mtRNA content over time between the 2 treatment arms. When arms were combined, both median mtDNA and mtRNA content showed statistically significant increases over the course of 48 weeks, from 206 to 278 copies/cell (P < .001) and from 154 to 288 copies/cell (P = .003), respectively. No statistically significant difference in mtDNA and mtRNA content was found between patients with and those without adverse events attributed to mitochondrial toxicity.


CONCLUSIONS
The observed increases in mtDNA and mtRNA content during the first year of treatment may represent a restorative trend resulting from suppression of HIV-1 infection, independent of the treatment used. Future studies should focus on well-defined mitochondrial toxicities and changes in these markers within the corresponding affected tissues simultaneously with those in PBMCs. Furthermore, with respect to studies of peripheral blood, mtDNA and mtRNA content in individual cell subtypes rather than in PBMCs may be better markers of toxicity and deserve further investigation.
Casula
Miriam
M
International Antiviral Therapy Evaluation Center, University of Amsterdam, The Netherlands. m.casula@iatec.com
Weverling
Gerrit Jan
GJ
Wit
Ferdinand W
FW
Timmermans
Eveline C
EC
Stek
Michael
M
Lange
Joep M
JM
Reiss
Peter
P
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D012313:RNA / Q000378:metabolism*; D000077278:RNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use*; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D012313:RNA; D018119:Stavudine