HIV-Induced Thymic Insufficiency and Aging-Related Immunosenescence on Immune Reconstitution in ART-Treated Patients.

The mechanisms underlying unsatisfactory immune reconstitution in HIV-1 positive patients under ART have not been fully elucidated, even after years of investigation. Thus, this study aimed to assess the correlation between age and thymic production profile, and its influence on inadequate immunological recovery. Here, 44 ART-treated patients with undetectable plasma HIV-1 load (<40 copies/mL) were classified as 31 immunological responders (IR) and 13 immunological non-responders (INR), according to their CD4+ T-cell count after 18 months of ART.

Thymic Exhaustion and Increased Immune Activation Are the Main Mechanisms Involved in Impaired Immunological Recovery of HIV-Positive Patients under ART.

Decades of studies in antiretroviral therapy (ART) have passed, and the mechanisms that determine impaired immunological recovery in HIV-positive patients receiving ART have not been completely elucidated yet. Thus, T-lymphocytes immunophenotyping and cytokines levels were analyzed in 44 ART-treated HIV-positive patients who had a prolonged undetectable plasma viral load. The patients were classified as immunological non-responders (INR = 13) and immunological responders (IR = 31), according to their CD4+ T cell levels.

Clinical-Epidemiological Characteristics and (rs12252) Variant Involvement in HIV-1 Mother-to-Children Transmission Susceptibility in a Brazilian Population.

Mother-to-children transmission (MTCT) is the main infection route for HIV-1 in children, and may occur during pregnancy, delivery, and/or postpartum. It is a multifactorial phenomenon, where genetic variants play an important role. This study aims at analyzing the influence of clinical epidemiological characteristics and a variant (rs12252) in interferon-induced transmembrane protein 3 (), a gene encoding an important viral restriction factor, on the susceptibility to HIV-1 mother-to-children transmission (MTCT).

Brief Report: Polymorphisms in TNF-α/TNFR1 Pathway Genes Are Associated With CD4+ T-Cell Recovery in HIV-1-Infected Individuals on Antiretroviral Therapy.

Background: Antiretroviral therapy (ART) is an important hallmark of HIV-1 treatment, enabling viral load suppression to undetectable levels and CD4+ T-cell recovery. However, some individuals do not recover the CD4+ T-cell count to normal levels, despite viral suppression. We hypothesize that variation in genes involved in extrinsic apoptosis pathways may influence interindividual immune recovery during ART.

HIV-1 Infection Transcriptomics: Meta-Analysis of CD4+ T Cells Gene Expression Profiles.

HIV-1 infection elicits a complex dynamic of the expression various host genes. High throughput sequencing added an expressive amount of information regarding HIV-1 infections and pathogenesis. RNA sequencing (RNA-Seq) is currently the tool of choice to investigate gene expression in a several range of experimental setting.

Differences in pyroptosis of recent thymic emigrants CD4+ T Lymphocytes in ART-treated HIV-positive patients are influenced by sex.

Pyroptosis cell death in recent thymus emigrants (RTE) CD4+ T lymphocytes plays an important role on HIV-1 infection as a cause of CD4+ T cell depletion, being influenced by several factors, among them, the sex. Thus, the aim of this study was evaluated pyroptosis levels in RTE CD4+ T lymphocytes of individuals under antiretroviral therapy (ART) stratified by sex. Thirty-seven ART-treated HIV-positive patients (22 females and 15 males) and 12 (seven females and five males) clinically health subjects were recruited.

CCR5 genotype and pre-treatment CD4+ T-cell count influence immunological recovery of HIV-positive patients during antiretroviral therapy.

This study was performed to assess the association of CCR5Δ32 and SDF1-3'A polymorphisms with immunological recovery failure and to investigate the influence of sociodemographic and clinical data on immune reconstitution in human immunodeficiency virus (HIV)-positive patients during antiretroviral therapy (ART). Two hundred and forty-eight HIV-positive patients under ART with undetectable plasma viral load (<40 copies/mL) were enrolled in this study and classified into two groups according to their CD4+ T-cell count changes: immunological responders (CD4+ T-cell count gain ≥ 200/µL or ≥ 30% compared with baseline) and immunological non-responders (CD4+ T-cell count gain < 200/µL or < 30% compared with baseline). DNA extraction was performed followed by CCR5Δ32 and SDF1-3'A genotyping.

Increased risk of dizziness in human immunodeficiency virus-infected patients taking zidovudine and efavirenz combination: a Brazilian cohort study.

Objectives: Neuropsychiatric adverse effects (NPAE) related to efavirenz, mainly dizziness, is detrimental to human immunodeficiency virus (HIV) treatment. Our study aims at evaluating if zidovudine use potentiates the risk of dizziness related to efavirenz when used together and whether there are significant differences in over time distribution of this NPAE and others relatively frequents regarding efavirenz regimen without zidovudine.

Methods: Human immunodeficiency virus-infected patients under efavirenz-containing different therapy were enrolled.

Immunological recovery failure in cART-treated HIV-positive patients is associated with reduced thymic output and RTE CD4+ T cell death by pyroptosis.

Despite more than three decades of studies and advances in combination antiretroviral therapy (cART) against human immunodeficiency virus (HIV), the mechanisms that precisely determine immune reconstitution failure have not been completely elucidated yet. Thus, this study aimed to investigate the thymic function, immune activation, and cell death by pyroptosis and apoptosis in virologically suppressed HIV-positive patients receiving cART. Immunophenotyping analyses were performed in 57 cART-treated HIV-infected patients with undetectable plasma viral load, who were classified as immunological nonresponders (INR = 29) and immunologic responders (IR = 28).

IL18 gene polymorphism and its influence on CD4+ T-cell recovery in HIV-positive patients receiving antiretroviral therapy.

Background: Pyroptosis has been reported to be critical in human immunodeficiency virus type 1 (HIV-1) pathogenesis and acquired immunodeficiency syndrome (AIDS) progression. Even after achieving viral suppression to undetectable levels during antiretroviral therapy (ART), exacerbated CD4+ T-cell death by pyroptosis has been suggested as one of the main causes of immunological non-response. Thus, variants in genes of pyroptosis pathway were studied in individuals with poor CD4+ T-cell reconstitution under antiretroviral therapy against HIV-1.

Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers.

Background: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated.

Objective: To identify predictive genetic markers of immune response to ART.

MicroRNA-Related Polymorphisms in Infectious Diseases-Tiny Changes With a Huge Impact on Viral Infections and Potential Clinical Applications.

MicroRNAs (miRNAs) are single-stranded sequences of non-coding RNA with approximately 22 nucleotides that act posttranscriptionally on gene expression. miRNAs are important gene regulators in physiological contexts, but they also impact the pathogenesis of various diseases. The role of miRNAs in viral infections has been explored by different authors in both population-based as well as in functional studies.

Lopinavir/Ritonavir Treatment Induces Oxidative Stress and Caspaseindependent Apoptosis in Human Glioblastoma U-87 MG Cell Line.

Background: Lopinavir and Ritonavir (LPV/r) treatment is widely used to prevent HIV mother-to-child transmission. Nevertheless, studies related to the impact of these compounds on patients, in particular in the foetus and newborns, are strictly required due to the controversial findings reported in the literature concerning possible neurologic side effects following the administration of these drugs.

Objectives: In our study, we evaluated the impact of LPV/r treatment on the human glioblastoma U- 87 MG cell line.

CUL5 and APOBEC3G Polymorphisms are Partially Implicated in HIV-1 Infection and Antiretroviral Therapy in a Brazilian Population.

Background: Host restriction factors are cellular proteins able to diminish or block viral replication in a cell-specific way.

Objective And Method: We evaluated the distribution of single nucleotide polymorphisms (SNPs) in APOBEC3G (rs3736685, rs2294367) and CUL5 (rs7117111, rs7103534, rs11212495) genes, among 264 HIV-1 infected (HIV-1+) and 259 unexposed- uninfected individuals from Northeast Brazil, looking for a possible association with susceptibility to HIV-1 infection, viral load during treatment, CD4+ T cell count and therapeutic success of the antiretroviral treatment.

Results: The rs11212495 CUL5 G allele and the CUL5 rs7103534-rs7117111 CG haplotype were more frequent among unexposed-uninfected than in HIV-1+ individuals, suggesting an association with a lower HIV-1 infection susceptibility.

Dendritic Cell-Based Immunotherapies to Fight HIV: How Far from a Success Story? A Systematic Review and Meta-Analysis.

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies.

TRIM5 gene polymorphisms in HIV-1-infected patients and healthy controls from Northeastern Brazil.

Humans show heterogeneity in vulnerability to HIV-1 infection, partially under control of genes involved in host immunity and virus replication. TRIM5α protein has restriction activity against replication of many retroviruses. Human TRIM5 gene single nucleotide polymorphisms have been reported as involved in susceptibility to HIV-1 infection.

Meta-analysis and time series modeling allow a systematic review of primary HIV-1 drug-resistant prevalence in Latin America and Caribbean.

Here we review the prevalence of HIV-1 primary drug resistance in Latin America and Caribbean using meta-analysis as well as time-series modeling. We also discuss whether there could be a drawback to HIV/AIDS programs due to drug resistance in Latin America and Caribbean in the next years. We observed that, although some studies report low or moderate primary drug resistance prevalence in Caribbean countries, this evidence needs to be updated.

NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection.

Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls).

DC-SIGN polymorphisms are associated to type 1 diabetes mellitus.

Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It has been hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immune response by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane protein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory response and T cells activation.

Association of CD209 and CD209L polymorphisms with tuberculosis infection in a Northeastern Brazilian population.

Tuberculosis (TB) caused by Mycobacterium tuberculosis, is major cause of morbidity and mortality worldwide. So far, many candidate genes have been investigated for their possible association with TB. Dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) and Liver/lymph node-specific intercellular adhesion molecule-grabbing non-integrin (L-SIGN), encoded by CD209 and CD209L genes respectively, are known for binding to M.