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Undetectable unintegrated HIV-DNA in persons with HIV: frequency and determinants.

Chiara Orlandi1,2, Benedetta Canovari3, Francesco Barchiesi3,4

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Undetectable unintegrated HIV-1 DNA (uDNA) in people with HIV (PWH) on suppressive therapy is linked to better immune health. This finding supports uDNA as a biomarker for recent infection events and immunological fitness.

Keywords:
Blood cellsHIV-1 infectionTotal HIV-DNAUnintegrated HIV-DNAViral reservoirqPCR

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Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Despite antiretroviral therapy (ART), HIV-1 persists as integrated and unintegrated DNA (uDNA).
  • Unintegrated DNA (uDNA) may indicate recent HIV-1 infection events below RNA assay detection limits.
  • Evaluating uDNA quantification in peripheral blood can identify individuals with no recent infection events.

Purpose of the Study:

  • To assess the performance of a uDNA quantification assay in people with HIV (PWH) on ART.
  • To identify individuals with undetectable uDNA, signifying no recent infection events.
  • To characterize clinical and immunological factors associated with uDNA detectability.

Main Methods:

  • Quantified total and unintegrated HIV-1 DNA using real-time PCR in 87 chronically treated PWH.
  • Analyzed clinical, virological, and immunological parameters against uDNA detectability.
  • Utilized samples from a real-world, retrospective cohort reflecting diverse ART regimens.

Main Results:

  • Unintegrated DNA (uDNA) was undetectable in 28% of samples, quantifiable in 13%, and detectable below limit in 60%.
  • Undetectable uDNA correlated with higher CD4+ T-cell nadir and current counts, and lower total HIV-1 DNA.
  • CD4+ T-cell nadir was the sole independent predictor of uDNA undetectability (p=0.001).

Conclusions:

  • A significant proportion of treated PWH had undetectable uDNA.
  • uDNA measurement complements HIV-1 RNA and CD4+ T-cell data, potentially identifying individuals with no recent infections and better immune status.
  • uDNA quantification shows promise as a biomarker for HIV-1 reservoir dynamics in clinical practice.