Modeling Efavirenz Diffusion in Lymph Nodes

• Jada Moore, Biomedical Engineering, Delaware State University

• Ryan Zurakowski, Biomedical Engineering, University of Delaware

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV. Due to its lipophilic nature, the drug can easily penetrate tissues and reach HIV reservoirs within a person’s lymph nodes. When efavirenz interacts with the virus, it binds to an enzyme essential for HIV replication, changing the enzyme’s shape and preventing the virus from easily replicating.

Data provided to our lab by collaborators showed the distribution of efavirenz throughout a monkey’s lymph node. Our goal was to determine whether the drug is uniformly distributed throughout the lymph node or if it concentrates near blood vessels. We fit the measured concentration data from the lymph nodes to a diffusion model, assuming the drug originated in the blood vessels, and estimated the diffusion length. A significant fraction of the data fell below the detection limit set by the smallest measurable value from the MALDI device. We then modeled this data using a left-censored log-normal noise model and compared this fit to a uniform distribution to determine which better described the data.

We found that the optimal fit to the data suggested a diffusion length much larger than a realistic amount. Based on the Akaike Information Criterion (AIC) model, the uniform distribution fit was superior. We can conclude that efavirenz diffuses freely throughout the lymph nodes rather than being only carried by the blood vessels, making it more effective for treating sites of the virus compared to other drugs.