Mitochondrial toxicity can be directly caused by HIV infection according to a Spanish study to be published in the September 1st edition of Clinical Infectious Diseases (now available on-line). It is already well established that nucleoside analogues (NRTIs) can damage the mitochondria, contributing to the development of lipodystrophy. This is the first study to show that HIV infection can cause mitochondrial damage, and the investigators suggest that the mitochondrial damage which HIV infection itself causes makes individuals more susceptible to the mitochondrial damage which NRTIs can cause.
Samples of peripheral blood mononuclear cells were obtained from 25 HIV-positive patients who had never taken anti-HIV drugs and 25 age and sex matched HIV-negative individuals. The HIV-positive patients had been diagnosed with HIV infection for a mean of 44 months, had a median CD4 cell count of 317 cells/mm3 and an HIV viral load of 100,000 copies/ml.
Investigators assessed mitochondrial DNA content, activity in the mitochondrial respiratory chain, the activity of a key enzyme involved in mitochondrial function, and lipid peroxidation, a marker of oxidative damage.
Mitochondrial DNA content was 23% lower in the HIV-positive patients (p
The activity of the enzyme glycerol-3-phosphate dehydrogenase, which is key to healthy mitochondrial function, was also inhibited by 22% (p
“The mechanism by which HIV causes mitochondrial DNA depletion is currently elusive”, note the investigators, but they believe that the spectrum of mitochondrial toxicity revealed by their study indicates that HIV causes “generalized mitochondrial damage.”
No significant association was found by the investigators between CD4 cell count and viral load and mitochondrial damage.
The investigators postulate that the negative effects of HIV on mitochondria could make HIV-positive patients more susceptible to the mitochondrial toxicities caused by NRTIs.
“We believe that the findings of the present study support the hypothesis that the effects of HIV on mitochondrial DNA content are nonspecific and would be better reflected in a scenario of more diffuse mitochondrial damage, probably associated with apoptotic changes caused by HIV,” conclude the investigators.
Miro O et al. Mitochondrial effects of HIV infection on the peripheral blood mononuclear cells of HIV-infected patients who were never treated with antiretrovirals. Clin Infect Dis 39 (on-line edition), 2004.