2026-05-19T01:29:19Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/263452025-12-18T12:59:59Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16963

00925njm 22002777a 4500 dc Lara-Aguilar, Violeta author Llamas-Adán, Manuel author Brochado-Kith, Oscar author Crespo-Bermejo, Celia author Grande-García, Sergio author Arca de Lafuente, Sonia author de Los Santos, Ignacio author Prado, Carmen author Alía, Mario author Sainz-Pinós, Coral author Fernandez-Rodriguez, Amanda author Martín-Carbonero, Luz author Madrid, Ricardo author Briz, Veronica author 2024-08-19 Background: Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC). Methods: Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen. Results: The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups. Conclusion: LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications. Lara-Aguilar V, Llamas-Adán M, Brochado-Kith Ó, Crespo-Bermejo C, Grande-García S, Arca-Lafuente S, de Los Santos I, Prado C, Alía M, Sainz-Pinós C, Fernández-Rodríguez A, Martín-Carbonero L, Madrid R, Briz V. Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era. J Biomed Sci. 2024 Aug 19;31(1):80. 10.1186/s12929-024-01064-z 1423-0127 1021-7770 Journal of biomedical science 39160510 https://hdl.handle.net/20.500.12105/26345 Activation HIV-1 Inflammation LLV Senescence Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era