HIV-DNA content in pTfh cells is associated with residual viremia in elite controllers

• Published in: AIDS (London) Vol. 35; no. 3; pp. 393 - 398
• Main Authors: García, Marcial, Morcilla, Vincent, Navarrete-Muñoz, Maria Ángeles, Fisher, Katie, Cabello, Alfonso, López-Bernaldo, Juan Carlos, De La Hera, Francisco, Barros, Carlos, Fernández-Guerrero, Manuel, Estrada, Vicente, Górgolas, Miguel, Benito, José Miguel, Palmer, Sarah, Rallón, Norma
• Format: Journal Article
• Language: English
• Published: England Lippincott Williams & Wilkins 01.03.2021; Copyright Wolters Kluwer Health, Inc
• Subjects: CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cross-Sectional Studies; DNA; HIV Infections - drug therapy; HIV-1 - genetics; Humans; Viral Load; Viremia
• ISSN: 0269-9370; 1473-5571; 1473-5571
• DOI: 10.1097/QAD.0000000000002776

OBJECTIVE:The source of residual HIV viremia is highly debated and its potential relationship with the HIV reservoir has not been clarified. Herein, we analyzed the cell-associated HIV-DNA content in two important cell compartments of the HIV reservoir, resting CD4+ T memory (Trm) and peripheral T follicular helper (pTfh) cells, and the association with the residual HIV viremia in individuals with spontaneous HIV replication control (elite controllers, EC group) and in subjects with ART-mediated HIV replication control (cART group). DESIGN:Cross-sectional study. METHODS:Seventeen chronically HIV-infected patients with suppressed HIV replication were included. Cell-associated HIV-DNA was measured by ultrasensitive digital-droplet-PCR in purified Trm and pTfh cells. Residual HIV plasma viremia was quantified using a single-copy assay with a sensitivity of 0.3 HIV-RNA copies/mL. RESULTS:A significant and positive correlation was demonstrated between HIV-DNA levels in pTfh cells and residual plasma viral load (rpVL) (rho=0.928, p = 0.008) in HIV+ elite controllers, but not in HIV+ treated patients, despite the lower levels of cell-associated HIV-DNA found in EC compared to cART patients in pTfh cells (176[77–882] vs. 608[361–860] copies/million cells respectively; p = 0.05). CONCLUSIONS:This association suggests that pTfh cells could have an important contribution to persistent viremia in elite controllers. This could be the consequence of a more limited control of HIV replication in EC individuals with higher transcriptional activity of HIV in pTfh cells of EC compared to that in cART patients.