Berta Pernas1, Ignacio Rego-Pérez2, Andrés Tabernilla1, Vanesa Balboa3, Sara Relaño4, Marta Grandal1, Manuel Crespo5, Álvaro Mena1, Ángeles Castro-Iglesias1, Francisco J Blanco2, Eva Poveda1. 1. Grupo de Virología Clínica, Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade de A Coruña (UDC), A Coruña, Spain. 2. Grupo de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade de A Coruña (UDC), A Coruña, Spain. 3. Unidad de Epidemiología Clínica y Bioestadística, Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain. 4. Plataforma de Genómica, Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complexo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain. 5. Internal Medicine Department, IIS Galicia Sur, Complexo Hospitalario Universitario de Vigo, Vigo, Spain.
Abstract
OBJECTIVES: To evaluate plasma mitochondrial DNA (mtDNA) levels among HIV-infected patients and its potential role as a biomarker of residual viral replication. METHODS: HIV-infected patients on follow-up at a reference hospital in north-west Spain were selected. DNA was isolated from plasma samples and mtDNA levels were assessed using a quantitative real-time PCR assay. HIV-RNA levels and CD4+ cell counts were evaluated in the same blood samples used for plasma mtDNA quantification. Epidemiological and clinical variables were included for the analysis. RESULTS: A total of 235 HIV-infected patients were included. Mean plasma mtDNA levels were 217 ± 656 copies/μL for naive (31.9%) and 364 ± 939 copies/μL for HIV-infected patients receiving ART and with suppressed viraemia (P = 0.043). Among the latter, mean plasma mtDNA levels were 149 ± 440 copies/μL for those with low-level viraemia (LLV; HIV-RNA 20-200 copies/mL), 265 ± 723 copies/μL for those with detected-not-quantified (DNQ) viraemia (HIV-RNA <20 copies/mL) and 644 ± 1310 copies/μL for those with not-detected (ND) viraemia. Of note, a linear trend (P = 0.006) was observed among virologically suppressed (LLV, DNQ and ND) patients. ND patients had higher mtDNA levels compared with LLV patients (P = 0.057). Moreover, mtDNA levels were inversely associated with HIV-RNA levels (Spearman's rho -0.191, P = 0.003) and directly associated with CD4+ counts (Spearman's rho 0.131, P = 0.046). CONCLUSIONS: Increased plasma mtDNA levels are associated with lower HIV-RNA levels and higher CD4+ cell counts. Among ART-suppressed patients, mtDNA levels were significantly higher in those with complete virological suppression (ND) than in those with LLV. These data suggest that plasma mtDNA levels might serve as a biomarker of residual HIV replication.
OBJECTIVES: To evaluate plasma mitochondrial DNA (mtDNA) levels among HIV-infected patients and its potential role as a biomarker of residual viral replication. METHODS: HIV-infected patients on follow-up at a reference hospital in north-west Spain were selected. DNA was isolated from plasma samples and mtDNA levels were assessed using a quantitative real-time PCR assay. HIV-RNA levels and CD4+ cell counts were evaluated in the same blood samples used for plasma mtDNA quantification. Epidemiological and clinical variables were included for the analysis. RESULTS: A total of 235 HIV-infected patients were included. Mean plasma mtDNA levels were 217 ± 656 copies/μL for naive (31.9%) and 364 ± 939 copies/μL for HIV-infected patients receiving ART and with suppressed viraemia (P = 0.043). Among the latter, mean plasma mtDNA levels were 149 ± 440 copies/μL for those with low-level viraemia (LLV; HIV-RNA 20-200 copies/mL), 265 ± 723 copies/μL for those with detected-not-quantified (DNQ) viraemia (HIV-RNA <20 copies/mL) and 644 ± 1310 copies/μL for those with not-detected (ND) viraemia. Of note, a linear trend (P = 0.006) was observed among virologically suppressed (LLV, DNQ and ND) patients. ND patients had higher mtDNA levels compared with LLV patients (P = 0.057). Moreover, mtDNA levels were inversely associated with HIV-RNA levels (Spearman's rho -0.191, P = 0.003) and directly associated with CD4+ counts (Spearman's rho 0.131, P = 0.046). CONCLUSIONS: Increased plasma mtDNA levels are associated with lower HIV-RNA levels and higher CD4+ cell counts. Among ART-suppressed patients, mtDNA levels were significantly higher in those with complete virological suppression (ND) than in those with LLV. These data suggest that plasma mtDNA levels might serve as a biomarker of residual HIV replication.
Authors: Eva Poveda; Andrés Tabernilla; Wendy Fitzgerald; Ángel Salgado-Barreira; Marta Grandal; Alexandre Pérez; Ana Mariño; Hortensia Álvarez; Nieves Valcarce; Juan González-García; José Ignacio Bernardino; Félix Gutierrez; Hisashi Fujioka; Manuel Crespo; Ezequiel Ruiz-Mateos; Leonid Margolis; Michael M Lederman; Michael L Freeman Journal: J Infect Dis Date: 2022-03-15 Impact factor: 7.759