A novel blood-based biomarker signature could offer a new way to detect HIV-2 and distinguish it from HIV-1, according to research published in the Journal of Clinical Microbiology.
Researchers developed a diagnostic model based on six circulating transfer RNAs (tRNAs), which achieved 100% accuracy, sensitivity, and specificity for HIV-2 in the samples evaluated. The findings provide proof of concept that host-derived tRNA expression profiles could serve as non-viral biomarkers for HIV diagnosis.
Although HIV-1 and HIV-2 share transmission and replication characteristics, distinguishing between the two has important implications for clinical management. HIV-2 generally has lower viral loads and slower disease progression, while differences in drug susceptibility mean that some antiretroviral treatments used against HIV-1 are ineffective against HIV-2.
Diagnosis can also be challenging when conventional viral markers are difficult to detect. The researchers therefore investigated whether changes in circulating tRNA expression could provide a host-derived marker of infection rather than relying directly on components of the virus.
An initial pilot analysis examined 88 tRNAs in plasma from four people with HIV-1, four with HIV-2, and four healthy controls. From this screening, 18 candidate tRNAs were selected and assessed in an independent cohort comprising 20 individuals in each of the three groups.
The researchers subsequently developed a diagnostic signature known as Model-II, consisting of six differentially expressed tRNAs: Leu-TAA, mt-Asp-GTC, mt-Ala-TGC, mt-Lys-TTT, mt-LeuT-AA, and Gly-CCC-1.
When evaluated in a further 24 independent samples, the model detected HIV-2 and differentiated it from HIV-1 and healthy controls with 100% accuracy, sensitivity, and specificity.
The researchers also assessed whether other blood-borne viral infections could interfere with the signature. No cross-reactivity with human T-cell lymphotropic virus, hepatitis B virus, or hepatitis C virus was observed, supporting the specificity of the model for HIV-2 within the samples studied.
The findings could be particularly relevant in situations where conventional viral markers are absent or unreliable. The authors highlighted increased use of pre-exposure prophylaxis (PrEP) as one setting in which new infections can present with low or undetectable viral markers.
Because the proposed test measures the host’s circulating tRNA expression rather than viral components directly, it could potentially provide a complementary route to identifying infection and differentiating HIV types.
However, the results represent an early proof of concept based on relatively small sample numbers. The six-tRNA signature will require validation in substantially larger and more diverse clinical populations before its diagnostic performance and potential role in routine HIV testing can be established.
Reference
0. A novel biomarker signature based on circulating transfer RNA (tRNA) can detect and differentiate HIV-2 infection from HIV-1. J Clin Microbiol. 2026;DOI: 10.1128/jcm.00378-26.
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