Following studies showing that cocaine influences the replication and transcription of HIV, a researcher at the George Washington University School of Medicine and Health Sciences (SMHS) was awarded more than $2.3 million from the National Institutes of Health to look deeper into the involved molecular mechanisms that allow this effect to happen.
Mudit Tyagi, PhD, assistant professor of medicine and of microbiology, immunology, and tropical medicine at SMHS, will lead the research team for the study. The team will characterize the signaling pathways and the downstream transcription factors that are selectively activated by cocaine.
"Anti-HIV drugs are effective in controlling HIV replication efficiently, but are unable to eradicate HIV," explained Tyagi. "Moreover, the blood brain barrier restricts the free-flow of anti-HIV drugs into the brain, which allows transient HIV replication in the brain."
Unlike the anti-HIV drugs that have trouble reaching the brain at consistent levels, cocaine more effectively targets the brain, and as Tyagi's lab has recently shown, can enhance the transcription and replication of HIV using specific mechanisms.
The goal of this research is to identify and characterize the cocaine-stimulated signaling and epigenetic pathways and use those findings to develop more effective biomarkers of cocaine use and therapeutics for cocaine-using HIV-infected and uninfected individuals.
Those potential biomarkers will make it easier to determine if someone has used cocaine. "Currently, to find if someone has used cocaine, one needs to assess cocaine metabolite levels in the blood, but they last for a very short amount of time," Tyagi explained. Cocaine-mediated epigenetic changes will last for a longer period.
In order to determine just how cocaine is able to affect the spread of HIV, the research team will study cell lines and primary cell samples from HIV patients who are and are not using the drug.
"While this research can impact HIV patients who use cocaine, it can also impact those not infected with HIV who are addicted to cocaine," Tyagi said. "Cocaine use can heighten the risk of getting other sexually transmitted diseases due to the involvement of unconventional and unprotected sexual activities by the drug-addicted population."