A research team led by Penn State Professor Dipanjan Pan has developed a new rapid test that can distinguish between true HIV infections and false positives caused by vaccine-induced antibodies. This development addresses a challenge in HIV vaccine trials, where some candidates can trigger immune responses that mimic actual infection in standard diagnostic tests.
Pan explained that while there is no approved vaccine for HIV yet, ongoing research involves various preventive and therapeutic strategies. However, these efforts are complicated by the issue of vaccine-induced seroreactivity or seropositivity (VISP), which occurs when participants in vaccine trials test positive for HIV-1 despite not being infected. According to Pan, "A direct consequence of this immunogenic overlap is that the vaccine can make a person test positive for HIV-1, even when they do not have the infection." He added, "This poses serious social, professional and personal consequences for those individuals. It can also make trial results difficult to interpret, slowing the progress toward widely available HIV vaccines."
The team partnered with the HIV Vaccine Trials Network, sponsored by the National Institutes of Health's Vaccine Research Center, to evaluate their device using 104 human blood samples. The device uses a combination of protein and nucleic acid analyses to produce results within five minutes. It correctly identified active HIV-1 infections 95% of the time and distinguished false positives related to vaccination 98% of the time.
"Despite continuous advancements in prevention and treatment, HIV remains a significant global health issue," said Pan. "Given this global burden, developing safe and effective vaccines is crucial for reducing HIV transmission rates and ultimately managing the epidemic."
Current diagnostics often require multistep procedures involving specialized equipment and trained personnel. The most accessible method to differentiate VISP from true infection relies on nucleic acid amplification tests, which are resource-intensive.
"The development of a rapid, affordable and reliable point-of-care diagnostic tool capable of distinguishing immune-induced responses from active HIV infection is essential to support the broader deployment of HIV vaccines and to address the limitations of existing technologies," Pan stated. He described their approach: "To address the laboratory testing challenges posed by this problem, we developed a test that simultaneous detects protein and nucleic acid markers within a single device."
The 3D-printed device filters plasma through channels over two test strips—one detecting protein biomarkers from antibodies (from either infection or vaccination) and another detecting RNA from virus particles. Pan noted: "By incorporating HIV-1 RNA detection, the testing platform provides a definitive indicator of active viral replication, which is absent in VISP cases. As such, this test can accurately discriminate between vaccine-induced responses and true infection."
Using artificial intelligence for analysis, results are delivered in five minutes with high sensitivity across all tested groups: non-vaccinated/HIV-negative; vaccinated/HIV-negative; non-vaccinated/HIV-positive; vaccinated/HIV-positive.
"Our proposed all-in-one testing platform represents a substantial advancement in HIV diagnostics, enabling accurate detection of active HIV infection while minimizing false positives due to VISP," said Pan. "The scalable design and relatively low-cost of the device make it an appealing solution for widespread adoption in both resource-rich and resource-limited environments."
The researchers published their findings on December 3 in Science Advances and have filed a patent for their technology.
Pan indicated future plans include refining the prototype for durability and expanding its capability to screen other pathogens. The team also envisions developing an at-home viral load test that could help patients monitor antiretroviral therapy effectiveness.
Contributors to this work included researchers from Penn State’s Departments of Chemistry, Biomedical Engineering, Radiation Oncology as well as collaborators from Vitruvian Bio, Indian Institute of Science Education and Research, Fred Hutchinson Cancer Center, Jordan University of Science and Technology among others.
Funding was provided by several U.S. government agencies including the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), Centers for Disease Control and Prevention (CDC), National Science Foundation (NSF), as well as Department of Defense’s Congressionally Directed Medical Research Program.
