Toll-like receptor agonists enhance HIV-specific T cell response mediated by plasmacytoid dendritic cells in diverse HIV-1 disease progression phenotypes.

Background: Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and -9 and translate this sensing into Interferon-α (IFN-α) production and T-cell activation. The understanding of the mechanisms involved in pDCs stimulation may contribute to HIV-cure immunotherapeutic strategies. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations in several HIV-1 disease progression phenotypes and in non HIV-1 infected donors.

High CD8 T cell percentage and HCV replication control are common features in HIV-1 controllers and HTLV-2-co-infected patients with a history of injection drug use.

HTLV-2/HIV-1-coinfected patients and HIV-infected patients with natural HIV-1 control show an immune capacity that allows some control of viral infections. These two groups of patients have showed an immune capacity that allows them to have some control over viral infections, very strong control of HIV-1 replication in the case of HIV-1 controllers. The purpose of this retrospective cross-sectional study was to compare viral and immunologic parameters between three cohorts of Caucasian adult HIV-1-infected patients, including HIV-1 controllers (29 patients), HTLV-2/HIV-1 chronic progressors (56 patients), and HIV-1 chronic progressors (101 patients), followed in two different tertiary University Hospitals in Spain.

Immune Correlates of Natural HIV Elite Control and Simultaneous HCV Clearance-Supercontrollers.

HIV-elite controllers are a minority group of HIV-infected patients with the ability to maintain undetectable HIV viremia for long time periods without antiretroviral treatment. A small group of HIV-controllers are also able to spontaneously clear the hepatitis C virus (HCV) whom we can refer to as "supercontrollers." There are no studies that explore immune correlates looking for the mechanisms implicated in this extraordinary phenomenon.

Proteomic Profile Associated With Loss of Spontaneous Human Immunodeficiency Virus Type 1 Elite Control.

Background: Elite controllers (ECs) spontaneously control plasma human immunodeficiency virus type 1 (HIV-1) RNA without antiretroviral therapy. However, 25% lose virological control over time. The aim of this work was to study the proteomic profile that preceded this loss of virological control to identify potential biomarkers.

Toll-Like Receptor 7 (TLR-7) and TLR-9 Agonists Improve Hepatitis C Virus Replication and Infectivity Inhibition by Plasmacytoid Dendritic Cells.

Plasmacytoid dendritic cells (pDCs) are innate immune cells with high antiviral activity triggered by Toll-like receptor 7 (TLR-7) and TLR-9 stimulation. Moreover, they are important mediators between innate and adaptive immunity. Although nowadays there is available an effective therapeutic arsenal against hepatitis C virus (HCV), a protective vaccine is not available.

Eradication of Hepatitis C Virus (HCV) Reduces Immune Activation, Microbial Translocation, and the HIV DNA Level in HIV/HCV-Coinfected Patients.

Background: There are contradictory data about the influence that hepatitis C virus (HCV) has on immune activation and inflammation in patients coinfected with human immunodeficiency virus (HIV) and HCV.

Methods: HIV/HCV-coinfected patients receiving antiretroviral treatment who achieved a sustained virological response with interferon-free regimens were consecutively enrolled in a prospective study. The following factors were assessed before, immediately after the end of, and 1 month after the end of therapy: expression of HLA-DR/CD38, PD-1, and CD57 on CD4+ and CD8+ T-cells; measurement of the total HIV DNA load in peripheral blood mononuclear cells; and determination of plasma levels of soluble CD14 (sCD14), lipopolysaccharide (LPS), 16S ribosomal DNA (rDNA), interleukin 6 (IL-6), D-dimers, and high-sensitivity C-reactive protein (hsCRP).

Increased CD127+ and decreased CD57+ T cell expression levels in HIV-infected patients on NRTI-sparing regimens.

Background: NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients.

Methods: Biomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14).

Association of heterozygous CCR5Δ32 deletion with survival in HIV-infection: A cohort study.

The role of a 32 base pair deletion in the CCR5 gene (CCR5Δ32) in HIV-disease progression and response to combined antiretroviral therapy (cART) is well established. However, the impact of CCR5Δ32 in the long-term survival pre-cART and after cART introduction in a large cohort of HIV-infected patients is unknown. We analyzed the association of CCR5Δ32 deletion in the long-term survival of HIV-infected patients recruited between June 1981 and October 2016 (n = 1006).

Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection.

HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC.

CCR5+ CD8 T-cell levels and monocyte activation precede the onset of acute coronary syndrome in HIV-infected patients on antiretroviral therapy.

Acute coronary syndrome (ACS) is nowadays one of the leading causes of morbid-mortality in HIV-infected population, but innate and adaptive immune mechanisms preceding this event are unknown. In this work we comprehensively and longitudinally observed, by multiparametric flow cytometry and following a case-control design, increased CCR5CD8 T-cells levels and monocytes expressing activation and adhesion markers in HIV-infected patients who are going to suffer ACS. In addition, we found direct associations between activated CD8 T-cells and myeloid cells that were only statistically significant in the group of patients with ACS and in the follow up time point just before the ACS.

HLA-B*57 and IFNL4-related polymorphisms are associated with protection against HIV-1 disease progression in controllers.

Background: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4T-cell decline. We investigated host genetic factors associated with protection against CD4T-cell loss in HIV-1-controllers.

Validation of the HIV Tropism Test TROCAI Using the Virological Response to a Short-Term Maraviroc Monotherapy Exposure.

TROCAI is a phenotypic tropism test developed using the virological response to a short-term exposure to maraviroc monotherapy (Maraviroc Clinical Test [MCT]). It was found that with TROCAI, a cutoff of <0.5% of dual/mixed viruses was needed to predict R5 HIV tropism.

Analysis of Non-AIDS-Defining Events in HIV Controllers.

Background: Human immunodeficiency virus (HIV) controllers have the striking ability to maintain viremia at extremely low or undetectable levels without antiretroviral treatment. Even though these patients have been widely studied, information about clinical outcomes, especially concerning to non-AIDS-defining events (nADEs), is scarce. We have analyzed the frequency and rate of nADEs and their associated factors in a large multicenter HIV controller cohort.

IFNL4 ss469415590 polymorphism is associated with unfavourable clinical and immunological status in HIV-infected individuals.

The IFNL4 ss469415590 polymorphism, in high linkage disequilibrium with the IL28B rs12979860 variant, has been associated with hepatitis C virus clearance. We evaluated whether ss469415590 is associated with clinical and immunovirological parameters in human immunodeficiency virus-infected subjects. We found an independent association of the IFNL4 ss469415590 polymorphism with higher prevalence of AIDS-defining illnesses and lower CD4 T cell numbers.

IFNγ⁻TNFα⁻IL2⁻MIP1α⁻CD107a⁺PRF1⁺ CD8 pp65-Specific T-Cell Response Is Independently Associated With Time to Death in Elderly Humans.

Persistent cytomegalovirus (CMV) infection has been suggested to be a major driving force in the immune deterioration and an underlying source of age-related diseases in the elderly. CMV antibody titers are associated with lower responses to vaccination, cardiovascular diseases, frailty, and mortality. CMV infection is also associated with shorter T-cell telomeres and replicative senescence.

TNF-α levels in HIV-infected patients after long-term suppressive cART persist as high as in elderly, HIV-uninfected subjects.

Background: Chronic and systemic inflammatory alterations occur in HIV-infected patients and elderly uninfected subjects and in both scenarios these alterations are associated with the development of chronic morbidities and mortality. However, whether the levels of inflammatory alterations in untreated HIV-infected patients and elderly individuals are similar is unknown. Moreover, whether long-term antiretroviral therapy normalizes inflammatory alterations compared with HIV-uninfected persons of different age is not known.