Quantitative HIV diagnostic that detects mutational burden

Value Proposition

• Straightforward and scalable: Researchers at Johns Hopkins have created a diagnostic assay that can quantify viral HIV particles in plasma and, at the same time, predict whether they are replication competent.
• Sensitive and low cost: This diagnostic tool can detect low levels of viremia and distinguish single mutations without the need for expensive and labor-intensive ultra-sensitive clinical assays or genome sequencing.

Unmet Need

•  Continuous antiretroviral therapy (ART), which suppresses viral replication, is the current standard of care for HIV patients.
• A subset of patients on ART experiences non-suppressible viremia (NSV), with persistent levels of HIV virus present in their bloodstream even when treatment is effective (Nature, 2023).
• Current clinical assays measure the levels of plasma HIV RNA, but do not provide genetic information about the integrity of viral RNA. Consequently, they cannot differentiate between defective proviruses, which might contribute to non-suppressible viremia (NSV).
• Therefore, there is a strong need to develop clinical assays to identify the root cause of non-suppressible viremia (NSV) to develop effective strategies to disrupt viral persistence and inform treatment outcomes.

Technology Description

Researchers at Johns Hopkins have developed a diagnostic assay that can precisely detect low levels of HIV RNA and assess the genetic integrity of the viral genome. The technique first concentrates HIV virions in plasma to improve detection, then amplifies a specific region of the HIV RNA genome using digital PCR. By using carefully designed primers and probes that bind to two specific regions of the genome—one of which is frequently mutated in defective HIV-1 proviruses—the assay can distinguish single mutations with 100% specificity without the need for sequencing and determine whether the genome is intact or defective.

Stage of Development: The current stage of development is in pre-clinical studies, as the researchers are currently testing and optimizing the assay on clinical samples.

Data Availability: See publication

Publication: 

1. Box, Julia R., et al. "5′ leader defects drive persistent HIV-1 viremia on long-term ART." Nature Communications 17.1 (2026): 4725