Grant: Doctoral Research Award - PA: Biomedical/Clinical HIV/AIDS Research

HIV and hepatitis C virus (HCV) share common routes of infection so that individuals are often infected with both. In BC, a third of HIV patients are co-infected with HCV. Half of HIV-infected individuals die of liver disease and of those, over 90% are co-infected with HCV. Co-infection increases liver damage and liver cancer, while decreasing HIV therapy tolerability and responsiveness to HCV therapy. HIV is treated with drug combinations referred to as highly active antiretroviral therapy (HAART). Nucleoside reverse transcriptase inhibitors (NRTIs) are used in HAART because they stop the HIV enzyme needed to replicate the virus. However, they may also stop the replication of human mitochondrial DNA (mtDNA) which is located within our mitochondria (organelles in cells that produce energy). NRTIs may promote changes in the mtDNA sequence (mutations) and/or removal of parts of the sequence (deletions). This type of mtDNA damage is associated with aging and age-related diseases. Our group has shown that, in some instances, HAART is associated with an increased amount of mtDNA, possibly because cells adapt to mitochondrial toxicity by making more mitochondria or because HAART prevents damaged mitochondria from being properly removed. Treatment for HCV includes Ribavirin, which is also associated with mitochondrial dysfunction. With this project, I will examine the effects of HAART and liver mitochondrial damage on HCV therapy outcome in HIV/HCV co-infected patients and on human liver cells grown in the lab. I will investigate mitochondrial changes and whether differences in mtDNA are due to cells making more mitochondria or cells being unable to properly remove damaged mitochondria. Our study participants have given a small liver sample prior to commencing their HCV therapy and one after completion. I will compare liver mtDNA damage before and after their treatment, and compare samples from patients who were on HAART during their HCV therapy versus those that were not.