ABSTRACT
People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.
Subject(s)
Coinfection , HIV Infections , HIV Seropositivity , HIV-1 , HTLV-II Infections , Hepatitis C , Humans , Human T-lymphotropic virus 2 , HIV-1/physiology , Proviruses , CD8-Positive T-Lymphocytes/pathology , Viral Load , Hepatitis C/complicationsABSTRACT
Up to 40% of newly diagnosed cases of HIV-1 infection are late diagnoses, with a profound decrease in CD4 cell counts in many cases. One-third of these individuals do not achieve optimal CD4 cell recovery (OR) after suppressive antiretroviral treatment (ART). This retrospective/longitudinal study of poor recovery (PR) included 79 HIV-1-infected individuals with CD4 count <200 cells/mm3 (25 PR and 54 OR) before ART. After suppressive ART, 21 PR and 24 OR individuals were further analysed, including paired samples. Selected miRs and plasma inflammatory markers were determined to investigate their potential predictive/diagnostic value for poor recovery. miR-192, IL-6 and sCD14 were independently associated with CD4 recovery before ART (p = 0.031, p = 0.007, and p = 0.008, respectively). The combination of these three factors returned a good discrimination (predictive value for PR) value of 0.841 (AUC, p < 0.001). After suppressive ART, miR-144 was independently associated with CD4 recovery (p = 0.017), showing a moderate discrimination value of 0.730 (AUC, p = 0.008) for PR. Our study provides new evidence on the relationship between miRs and HIV-1 infection that could help improve the management of individuals at HIV-1 diagnosis. These miRs and cytokines signature sets provide novel tools to predict CD4 cell recovery and its progression after ART.
Subject(s)
Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , HIV Infections/immunology , Interleukin-6/metabolism , Lipopolysaccharide Receptors/metabolism , MicroRNAs/metabolism , Adult , Exosomes/metabolism , Female , HIV Infections/genetics , Humans , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , ROC Curve , SolubilityABSTRACT
Exosome-derived miR-21 was independently associated with CD4 T cell decline in HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137-0.994, p = 0.049). Also, a negative correlation between miR-21 expression and MCP-1 level was found (r = -0.649, p = 0.020), while no correlation between soluble biomarkers or cellular immune activation was found.
