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

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.