Plasma Cytochrome C Level As Biomarker For Monitoring Artinduced Mitochondrial Toxicity

ABSTRACT HIV/AIDS is a major public health issue, having killed several millions of people, with subSaharan Africa mostly affected. Management of HIV infection, over the past decades, has been carried out using antiretroviral (ARV) drugs. Although antiretroviral therapy (ART) has decreased morbidity and mortality from HIV, long term therapy is associated with toxicity and severe side effects. These side effects have been attributed in part to ART-induced mitochondrial toxicity due to mitochondrial enzyme inhibition and induction of apoptosis. Diagnosing ART toxicity is, however, challenging as there is no standard test due to absence of reliable diagnostic biomarker. Cytochrome c (Cyt-c), a pro-apoptotic protein, has been suggested as a potential biomarker for monitoring ART-induced toxicity in a pilot study in African-Americans. However, for plasma Cyt-c to be used as a universal biomarker for ART toxicity, the study must be repeated among different populations. The present study therefore aimed at determining whether plasma Cyt-c levels correlate with duration of ART in Ghanaian HIV patients. Ghanaian HIV patients (n = 80) on ART were recruited and 60 were screened for symptoms of ART toxicity. Plasma levels of Cyt-c were measured. Out of the 60 participants, 11 (18.3%) were found with symptom of myopathy, 12 (20%) with pancreatitis, 21 (35%) with hyperlipidaemia and 36 (60%) with at least one of the symptoms. In general, 60% was observed to show toxicity and 40% to be without toxicity. Concentration of plasma Cyt-c was higher (0.122 ng/ml) in patients with toxicity than in those without toxicity (0.05 ng/ml) though the difference was not statistically significant (p = 0.148). No correlation was found between plasma Cyt-c level and duration of ART, age and CD4 counts. Plasma Cyt-c level could be used as an alternative approach to investigate toxicity associated with ART but this requires further studies.