Since the human immunodeficiency virus (HIV) was identified in 1983, roughly 91.4 million people around the world have contracted the virus and an additional 44.1 million have died from related causes. Currently, nearly 40 million people worldwide are living with HIV-1, the version of the virus that causes more than 95% of infections. While significant progress has been made in HIV vaccine research, according to Penn State Professor Dipanjan Pan, there is currently no approved vaccine for HIV. Research is ongoing, though, he said, with multiple preventive and therapeutic strategies under investigation - but some vaccine candidates can cause participants to falsely test HIV-positive, complicating diagnosis and clinical management.
To solve this issue, Pan and his team developed a new approach capable of differentiating active HIV infection from false positives - which could potentially accelerate vaccine development and testing, Pan said. The researchers partnered with the HIV Vaccine Trials Network, which is sponsored by the National Institutes of Health's Vaccine Research Center, to test 104 human blood samples with their new device. The device, which employs a combination of analyses to produce results in just five minutes, correctly identified those with active HIV-1 infection 95% of the time and those without active infection but with vaccine-induced molecules that could trigger a false positive, 98% of the time. That's on par or better than every current approach, Pan said.
The researchers published their work today (Dec. 3), for which they have also filed a patent, in Science Advances.
"Despite continuous advancements in prevention and treatment, HIV remains a significant global health issue," said Pan, the Dorothy Foehr Huck & J. Lloyd Huck Chair Professor in Nanomedicine and professor of nuclear engineering and of materials science and engineering. "Given this global burden, developing safe and effective vaccines is crucial for reducing HIV transmission rates and ultimately managing the epidemic."
HIV vaccines under development are intentionally designed to induce the production of antibodies that target key HIV antigens, which are proteins on the virus's surface that identify it as a threat to the immune system. Antibodies can bind to these antigens and help render the virus inert, meaning it can no longer infect a host's cells. The antigens are also what diagnostic tests detect to confirm an infection.
"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," Pan said, explaining that this phenomenon is called vaccine-induced seroreactivity or seropositivity (VISP) and refers to positive results on serologic - components of blood - antibody-based HIV tests. "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."
According to Pan, across various HIV vaccine trials, false positives or VISP occurs in anywhere from .4% to 95% of tests. The broad range depends on patient demographics, types of diagnostic tests used, vaccine design and several other variables. This is further complicated by seroreactivity, or the presence of antibodies in a blood sample that are left over from a vaccine-induced immune response or a prior infection. Like VISP, seroreactivity can also trigger false positives with antibodies persisting for more than two decades in some cases.
"VISP and seroreactivity are not just technical nuisances; they can lead to ongoing misdiagnosis with broad effects on individuals and populations, such as psychological distress and societal challenges, including misunderstanding within families and communities," Pan said. "They can also create logistical barriers, especially for health care workers who might be disqualified from donating blood, bone marrow or other organs and face additional complications with insurance, military service, employment, travel, immigration or pregnancy."
Pan noted that VISP is often perceived as a risk for participating in vaccine trials, which limits recruitment. Once a vaccine is approved and administered, Pan said, the issue doesn't abate, as VISP could skew HIV incidence data; necessitate unnecessary medical follow-up or treatment; complicate population vaccination efforts; or even obscure genuine HIV infection outbreaks.
