According to the World Health Organization, 38.4 million people worldwide in 2021 were living with the human immunodeficiency virus (HIV), which causes AIDS. However, there has been a 32% decrease in the number of HIV infections and 52% fewer deaths since 2010. While improved treatment and therapy have contributed to the decreases, early HIV diagnosis remains an issue.
Chemical and Biomedical Engineering Assistant Professor Chang Liu is currently working on research that aims to develop a nanopore-based HIV self-test that could help lower transmission rates and allow for early treatment to reduce the chances of developing AIDS.
Liu’s three-year research is supported by a $1.2 million grant from the National Institute of Allergy and Infectious Diseases. He will work alongside Dr. Helmut Albrecht, an infectious disease expert and professor of internal medicine at the University of South Carolina School of Medicine. Albrecht also serves as medical director of the Center for Infectious Disease Research and Policy for Prisma Health and USC.
Liu previously studied biosensing technologies, which is the detection of target molecules based on principles used by a living system. After applying his biosensing work to disease detection, his focus changed to tuberculosis. This was when he learned that tuberculosis is the number one cause of death in HIV-infected individuals.
“I gradually started to work on HIV and once I joined the college in 2018, I immediately contacted Dr. Albrecht, and we talked about the challenges with HIV monitoring and diagnosis in frontline clinics,” Liu says. “We figured this was something where engineers could help. Early and more accessible detection is the motivation for launching this project.”
According to Liu, most HIV physicians assume that nucleic acids are more sensitive biomarkers than proteins such as antigens and antibodies. But this is not true biologically because when an infection develops, both nucleic acids and proteins are released simultaneously. The real reason is that current technology better detects nucleic acids at an earlier stage than proteins.
There are currently some HIV self-tests, but it doesn't help for HIV control through early detection. Roughly 30% to 50% of new HIV cases every year in the U.S. are from those who didn't know they got infected.
- Chang Liu
Liu says that there is a problem because of the lack of sensitive technology to detect proteins. To help alleviate that issue, he led a research team that developed a Chemistry Amplified Nanopore (CAN) assay for ultrasensitive detection of HIV infection. He plans to transfer the assay into a small, automated device that is affordable and as reliable as a lab-based assay for patients to self-test by monitoring and quantifying their HIV-related protein level. Liu aims for the device to detect the antigen p24, which can indicate early HIV infection and progression. It may also reflect the effectiveness of HIV therapy.
“The traditional p24 detection method is the enzyme-linked immunosorbent assay (ELISA), but it’s not as sensitive as our CAN assay. By using our assay, we've demonstrated in the same patient cohort that we can detect it more accurately and allow p24 to be utilized and be as good as nucleic acids,” Liu says.
Liu has demonstrated the effectiveness of the CAN assay in the lab. But he admits that since ELISA can only be performed in lab and clinical settings, no self-testing technology exists. And while HIV antibody tests can confirm that someone has been infected with HIV, the antibodies develop after a month, which is considered a late detection.
“There are currently some HIV self-tests, but they are paper-based and not sensitive. It doesn't help for HIV control through early detection because roughly 30% to 50% of new HIV cases every year in the United States are from those who didn't know they got infected,” Liu says.
Liu’s research project also intends to develop the CAN assay into a point of care test. The small, portable and automated HIV self-test will allow patients, front line nurses and others to use the simplified device.
“It can be hard to handle complicated machines, but this device simply will have only one push button. We’ve already demonstrated the chemistry part and the assay’s performance in patients. Now we're moving everything into a small onboard automated device,” Liu says.
Earlier this year, Liu and Albrecht recruited 118 patients and demonstrated their first stage of research by measuring their blood in the lab with hands-on assays. Once a prototype for an HIV self-test device is developed, Liu intends to enroll 400 patients at Prisma Health to use the device under nursing supervision.
“It's fascinating that these nanopore technologies have been popping up internationally and having somebody [Liu] in our backyard who's at the forefront is great,” Albrecht says. “It’s still proof of concept but has enormous abilities to be a better point of care test. And there's commercial interest in this, so it’s certainly doable outside of a lab. Having this type of test could potentially close a gap down the road.”
From a user perspective, Liu envisions that the HIV self-test device will be similar to one that diabetes patients use to check their blood sugar level. But Liu’s device will be nanopore-based, which is a single molecule counter.
“We're using an entirely different technology. You would still be using a blade to get the finger blood, but there’s a tube to collect blood that’s then inserted into the device. It will automatically place the blood into a reaction chamber where the antigen molecules will be extracted from the blood and converted into a detection probe. The detector will quantify the probe to reflect the proteins in the original blood sample,” Liu says.
Liu is excited to continue working with Albrecht on a translational device and can see a pathway to bring this new technology directly from the labs and clinics to patients.
“As engineers, we want to see the technology not only work in the lab but also the real world. That's the ultimate and best reward,” Liu says. “I think this is a fantastic project because being able to have an HIV self-test device is something that no one thought of only a couple of years ago.”