Munoz-Muela, Esperanza , Trujillo-Rodriguez, Maria , SERNA GALLEGO, ANA DEL ROSARIO, Saborido-Alconchel, Abraham , Gasca-Capote, Carmen , Alvarez-Rios, Ana , Ruiz-Mateos, Ezequiel , Sviridov, Dmitri , Murphy, Andrew J. , Lee, Man K. S. , Lopez-Cortes, Luis F. , Gutierrez-Valencia, Alicia
No
EBioMedicine
Article
Científica
1
1
10.8
01/10/2024
001314433400001
Background: Among people living with HIV-1 (PHIV), immunological non-responders (INR) experience incomplete immune recovery despite suppressive antiretroviral treatment (ART), facing more severe non-AIDS events than immunological responders (IR) due to higher chronic immune activation and inflammation (cIA/I). We analyzed the HIV-1 reservoir and immunometabolism in monocytes as a source of cIA/I. Methods: Cross-sectional study in which 110 participants were enrolled: 25 treatment-na & iuml;ve; 35 INR; 40 IR; and 10 healthy controls. Cell-associated HIV-1-DNA (HIV-DNA) and -RNA (HIV-RNA) were measured in FACS-isolated monocytes using digital droplet PCR. Intact, 5 ' deleted, and 3 ' deleted proviruses were quantified by the intact proviral DNA assay. Systemic inflammation, monocyte immunophenotype, and immunometabolism were characterized by immunoassays, flow cytometry, and real-time cellular bioenergetics measurements, respectively. Findings: Monocytes from INR harbor higher HIV-RNA and HIV-DNA levels than IR. HIV-RNA was found in 14/21 treatment-na & iuml;ve [2512 copies/10(6) TBP (331-4666)], 17/33 INR [240 (148-589)], and 15/28 IR [144 (15-309)], correlating directly with sCD163, IP-10, GLUT1(high) cells and glucose uptake, and inversely with the CD4(+)/CD8(+) ratio. HIV-DNA was identified in all participants with detectable HIV-RNA, with intact provirus in 9/12 treatment-na & iuml;ve [13 copies/10(6) monocytes (7-44)], 8/14 INR [46 (18-67)], and 9/13 IR [9 (7-24)]. INR presented glucose metabolism alterations and mitochondrial impairment; decreased coupling efficiency and BHI, and increased mitochondrial dysfunction inversely correlating with the CD4(+)/CD8(+) ratio. Interpretation: HIV-RNA, more than HIV-DNA, in monocytes and their altered metabolism are factors associated with the higher cIA/I that characterize INR.
Immunological non-responders; Monocytes; HIV-1 reservoir; Immunometabolism; Immune activation and inflammation