Mitochondrial DNA depletion in HIV-infected patients is more pronounced with chronic hepatitis C and enhanced following treatment with pegylated interferon plus ribavirin.
BACKGROUND
Mitochondrial DNA (mtDNA) damage seems to be responsible for many of the toxicities associated with the long-term use of nucleoside analogues in HIV-infected patients. These adverse effects, mainly lipoatrophy, seem to be even more pronounced in subjects with hepatitis C virus (HCV) co-infection. However, there is no information about a possible additive effect of HCV on mtDNA depletion nor about the impact of ribavirin use in HIV/HCV-coinfected individuals.


METHODS
mtDNA was measured in peripheral blood mononuclear cells (PBMC) collected from 192 individuals classified into 4 groups: HIV-neg/HCV-neg (control group, n = 11), HIV-pos/HCV-neg (56), HIV-neg/HCV-pos (18) and HIV-pos/HCV-pos (107). A duplex real-time NASBA assay was used to quantify mtDNA on maximal platelet-depleted specimens and all experiments were run in duplicate. The mtDNA copy number per cell was estimated taking as reference the nuclear DNA copy number.


RESULTS
The mean mtDNA values in the control group was 757 copies/cell, while it was 428, 349 and 296 for HIV-pos, HCV-pos and HIV/HCV-coinfected individuals, respectively (P < 0.001 for all groups relative to the control group). No significant differences were observed when comparing patients with HIV or HCV infections alone, but coinfected individuals showed a lower mtDNA copy number than patients infected with HIV (P < 0.001) or with HCV (P = 0.089). In a subset of 18 patients with HIV/HCV-coinfection, treatment with pegylated interferon plus ribavirin produced a further reduction in mtDNA (mean value, 189 copies/cell; P = 0.009).


CONCLUSIONS
HIV and HCV may independently cause mtDNA depletion in PBMC. Coinfection may result in more pronounced mtDNA depletion. The administration of interferon plus ribavirin may further enhance mtDNA depletion. These findings may explain the greater risk of lipoatrophy of antiretroviral therapy in HIV-infected patients with HCV coinfection and why anti-HCV therapy may aggravate this effect.
de Mendoza
Carmen
C
Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Sánchez-Conde
Matilde
M
Timmermans
Eveline
E
Buitelaar
Marije
M
de Baar
Michel P
MP
Gonzalez-Lahoz
Juan
J
Soriano
Vincent
V
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000503:physiopathology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007372:Interferons / Q000009:adverse effects*; D008297:Male; D011092:Polyethylene Glycols / Q000009:adverse effects; D012254:Ribavirin / Q000009:adverse effects*
D000998:Antiviral Agents; D004272:DNA, Mitochondrial; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons