Munoz-Muela, Esperanza , Mejias-Trueba, Marta , SERNA GALLEGO, ANA DEL ROSARIO, Saborido-Alconchel, Abraham , Fernandez-Perez, Susana , Herrero, Marta , Sotomayor, Cesar , Gutierrez-Valencia, Alicia , Trujillo-Rodriguez, Maria , Lopez-Cortes, Luis F.
No
J. Infect. Dis.
Article
Científica
08/04/2025
001461138300001
2-s2.0-105010619987
Background New nucleos(t)ide reverse transcriptase inhibitors are considerably less toxic than their predecessors, but they may not be entirely devoid of toxicity. However, their effect in healthy adults remains unknown. We aimed to analyze the impact of tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC)-based preexposure prophylaxis (PrEP) on mitochondria of subjects at high risk of human immunodeficiency virus type 1 infection.Methods This was an observational, prospective study of 59 healthy adults enrolled in the PrEP program at Virgen del Roc & iacute;o University Hospital. Mitochondrial DNA and common deletion 4977 were measured using digital droplet polymerase chain reaction. Mitochondrial density, membrane potential, oxidative stress, metabolic profile, and morphology were assessed by flow cytometry, real-time cellular bioenergetics measurements, and transmission electron microscopy, respectively, at baseline and after 12 months. Values were compared by the Wilcoxon test, and correlations between variables were assessed using the Spearman rank correlation coefficient (rho).Results Our results showed that after 12 months, TDF/FTC induced a mitochondrial oxidative stress increase in myeloid and lymphoid populations. Mitochondrial density decreased in CD8+ T cells and natural killer cells, while mitochondrial membrane potential was augmented in all lymphoid populations. Cell bioenergetic health was compromised, evidenced by reduced oxygen consumption rate, declined adenosine triphosphate production, and impaired response capacity to an energetic demand. Changes in the shape, membrane integrity, cristae structure, size, and distribution of the mitochondria throughout the cytoplasm were also observed. All participants experienced alterations in 1 or more measured parameters.Conclusions TDF/FTC-based PrEP induces mitochondrial toxicity in healthy subjects after 12 months of treatment, negatively affecting mitochondrial function and morphology. Twelve months on nucleos(t)ide reverse transcriptase inhibitor-based preexposure prophylaxis is not without mitochondrial toxicity in healthy young men, consistent with available evidence in vitro or in people with HIV-1. This treatment induces mitochondrial impairment at the molecular, functional, and morphological levels.
preexposure prophylaxis; mitochondrial toxicity; nucleos(t)ide reverse transcriptase inhibitors; mitochondrial respiration; healthy subjects