ArticleThe Journal of infectious diseases2026
Mitochondrial DNA Fragment Dynamics in Acute and Chronic Human Immunodeficiency Virus: Insights From Human and Nonhuman Primate Models.
Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCirculating cell-free mitochondrial DNA (ccf-mtDNA) fragments are released into the bloodstream following cell death and are associated with comorbidities seen in people with HIV-1 (PWH). However, ccf-mtDNA dynamics in acute and chronic HIV infection remain unclear.
methodsWe quantified short and long ccf-mtDNA fragments in serum from 2 cohorts of PWH and people without HIV (PWoH), collected at 1, 3, and 5 years in the first cohort (N = 890) and 1 and 5 years in the second (N = 427). Mixed-effect linear regression models were used to analyze longitudinal associations of ccf-mtDNA levels with HIV status and markers (CD4-cell count, viral load). In parallel, we examined ccf-mtDNA levels in nonhuman primates (NHPs) before and after simian immunodeficiency virus (SIV) infection and following 3 and 6 months of ART.
resultsIn both human cohorts, PWH had significantly lower levels of short and long ccf-mtDNA fragments compared with PWoH. Individuals with lower CD4 T-cell counts exhibited further reductions in ccf-mtDNA levels. In NHPs, short ccf-mtDNA levels increased after infection, peaking before ART initiation (P = .001), and subsequently declined, reaching levels below baseline after 6 months on ART. Long ccf-mtDNA fragments remained stable during the early post-ART phase but declined significantly by 6 months (P = .02).
conclusionsChronic HIV infection and treated SIV infection are associated with reduced ccf-mtDNA levels, particularly in advanced disease stages. Further research is needed to clarify their role in immune activation, chronic inflammation, and aging-related comorbidities in PWH and their applicability as clinically relevant biomarkers of these processes.
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