LTNP

OBJECTIVE: We utilize a large retrospective study cohort derived from electronic medical records (EMR) to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda. METHODS: EMRs from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters...

BACKGROUND: COVID-19 is a highly infectious respiratory disease that can manifest in various clinical presentations. Although many studies have reported the lipidomic signature of COVID-19, the molecular changes in asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain elusive. METHODS: This study combined a comprehensive lipidomic analysis of 220 plasma samples from 166 subjects: 62 healthy controls, 16 asymptomatic infections, and 88 COVID-19 patients...

The gut is a major reservoir in HIV-infected individuals on antiretroviral therapy (ART) and in long-term non-progressors (LTNPs). Whether ART reduces gut infection and reservoirs in LTNPs is unknown. Herein, SIV-infected LTNP Rhesus macaques were treated with short- or long-term ART, and SIV envelope gp120 sequences obtained from single genome amplification were analyzed before and after ART in peripheral blood and the intestine. Although ART does not eliminate SIV in these LTNPs, a longer ART period dramatically reduces SIV infection in the gut...

Different phenotypes exhibiting no evidences of disease progression have been described in ART-naïve HIV-1 positive individuals. Long-term non progressors (LTNP) and elite controllers (EC) are low frequent examples of immunological and virological control in HIV-1 positive subjects, respectively. The combination of both phenotypes is even less frequent and studied despite being considered as models of HIV-1 functional cure. A multicenter, prospective study in retrospect including clinical and epidemiological data collected from 313 LTNP of 21 Spanish hospitals was carried out...

Identifying epitope targets by studying the native antibody (Ab) response can identify potential novel vaccine constructs. Studies suggest that long-term non-progressor (LTNP) subjects have inherent immune mechanisms that help to control viremia and disease progression. To explore a role for antibodies (Abs) in LTNP progression, our lab has previously characterized a number of highly mutated Abs that target conformational epitopes of the human immunodeficiency virus (HIV) envelope protein from a single LTNP subject (10076)...

This article reviews the main discoveries achieved by transcriptomic approaches on HIV controller (HIC) and long-term non-progressor (LTNP) individuals, who are able to suppress HIV replication and maintain high CD4+ T cell levels, respectively, in the absence of antiretroviral therapy. Different studies using high throughput techniques have elucidated multifactorial causes implied in natural control of HIV infection. Genes related to IFN response, calcium metabolism, ribosome biogenesis, among others, are commonly differentially expressed in LTNP/HIC individuals...

This work was carried out in order to broaden the application field of lignin and improve its additional value. The degraded deep eutectic solvent lignin-grafted poly( N -vinyl caprolactam) (DES-lignin- g -PNVCL) was synthesized by using modified DES-lignin and NVCL via activators regenerated by electron transfer-atom transfer radical polymerization (ARGET-ATRP). Aspirin was coated with DES-lignin- g -PNVCL through self-assembly by an ethanol/water anti-solvent method to obtain lignin thermosensitive polymer nanoparticle coated aspirin (aspirin@LTNP)...

In studies on monoclonal IgG antibodies (mAbs) from long-term non-progressors (LTNPs), our laboratory has previously described highly mutated Abs against a complex conformational epitope with contributions from both gp41 the N terminal and C terminal heptad repeat helices. Despite using the VH1-2 gene segment, known to contribute to some of the broadest neutralizing Abs against HIV, members of these Abs, termed group 76C Abs, did not exhibit broad neutralization. Because of the high number of mutations and use of VH1-2, our goal was to characterize the non-neutralizing functions of Abs of group 76C, to assess if targeting of the epitope correlates with LTNP, and to assess the maturation of these Abs by comparison to their predicted common ancestor...

The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity...

This study reports on HIV-specific T cell responses in HIV-1 infected Viremic Non-Progressors (VNPs), a rare group of people living with HIV that exhibit asymptomatic infection over several years accompanied by stable CD4+ T cell counts in spite of ongoing viral replication. We attempted to identify key virus-specific functional attributes that could underlie the apparently paradoxical virus-host equilibrium observed in VNPs. Our results revealed modulation of HIV-specific CD4+ and CD8+ effector T cell responses in VNPs towards a dominant non-cytolytic profile with concomitantly diminished degranulation (CD107a+) ability...

The understanding of HIV-1 pathogenesis and clinical progression is incomplete due to the variable contribution of host, immune, and viral factors. The involvement of viral factors has been investigated in extreme clinical phenotypes from rapid progressors to long-term non-progressors (LTNPs). Among HIV-1 proteins, the envelope glycoprotein complex (Env) has been concentrated on in many studies for its important role in the immune response and in the first steps of viral replication. In this study, we analyzed the contribution of 41 Envs from 24 patients with different clinical progression rates and viral loads (VLs), LTNP-Elite Controllers (LTNP-ECs); Viremic LTNPs (vLTNPs), and non-controller individuals contemporary to LTNPs or recent, named Old and Modern progressors...

BACKGROUND: Long-Term Non-Progressors (LTNPs) are untreated Human Immunodeficiency virus type 1 (HIV-1) infected individuals able to control disease progression for prolonged periods. However, the LTNPs status is temporary, as viral load increases followed by decreases in CD4 + T-cell counts. Control of HIV-1 infection in LTNPs viremic controllers, have been associated with effective immunodominant HIV-1 Gag-CD8 + T-cell responses restricted by protective HLA-B alleles. Individuals carrying HLA-B*14:02 control HIV-1 infection is related to an immunodominant Env-CD8 + T-cell response...

BACKGROUND: The latent reservoir of Human Immunodificiency Virus-1 (HIV-1) has been a major barrier to the complete eradication of HIV-1 and the development of HIV therapy. Long-term non-progressors (LTNPs) are a rare group of patients with HIV-1 who can spontaneously control HIV-1 replication without antiretroviral therapy. Transcriptome analysis is necessary to predict the pathways involved in the natural control of HIV-1, elucidate the mechanisms involved in LTNPs, and find biomarkers for HIV-1 reservoir therapy...

Human leucocyte antigen (HLA) class I molecules present endogenously processed antigens to T-cells and have been linked to differences in HIV-1 disease progression. HLA allelotypes show considerable geographical and inter-individual variation, as does the rate of progression of HIV-1 disease, with long-term non-progression (LTNP) of disease having most evidence of an underlying genetic contribution. However, most genetic analyses of LTNP have occurred in adults of European ancestry, limiting the potential transferability of observed associations to diverse populations who carry the burden of disease...

BACKGROUND: Some long-term non-progressors (LTNPs) have decreasing CD4+ T cell counts and progress to AIDS. Exploring which subsets of CD4+ T cell decreasing and the determinants associated with the decay in these patients will improve disease progression surveillance and provide further understanding of HIV pathogenesis. METHODS: Twenty-five LTNPs infected with HIV by blood products were classified as decreased (DG) if their CD4+ cell count dropped to < 400 cells/μL during follow-up or as non-decreased (non-DG) if their CD4+ cell count was ≥400 cells/μL...

Autophagy is a lysosomal-dependent degradative mechanism essential in maintaining cellular homeostasis, but it is also considered an ancient form of innate eukaryotic fighting against invading microorganisms. Mounting evidence has shown that HIV-1 is a critical target of autophagy that plays a role in HIV-1 replication and disease progression. In a special subset of HIV-1-infected patients that spontaneously and durably maintain extremely low viral replication, namely, long-term nonprogressors (LTNP), the resistance to HIV-1-induced pathogenesis is accompanied, in vivo, by a significant increase in the autophagic activity in peripheral blood mononuclear cells...

Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4...

HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14++ CD16+ monocytes were found to accumulate and CD11c+ conventional dendritic cells (cDC) to be depleted in a Portuguese cohort of people living with HIV-2 (PLWHIV-2), compared to blood bank healthy donors (HD). We studied more precisely classical monocytes; CD16+ inflammatory (intermediate, non-classical and slan+ monocytes, known to accumulate during viremic HIV-1 infection); cDC1, important for cross-presentation, and cDC2, both depleted during HIV-1 infection...

Sow fertility traits, such as litter size and the number of lifetime parities produced (reproductive longevity), are economically important. Selection for these traits is difficult because they are lowly heritable and expressed late in life. Age at puberty (AP) is an early indicator of reproductive longevity. Here, we utilized a custom Affymetrix single-nucleotide polymorphisms (SNPs) array (SowPro90) enriched with positional candidate genetic variants for AP and a haplotype-based genome-wide association study to fine map the genetic sources associated with AP and other fertility traits in research (University of Nebraska-Lincoln [UNL]) and commercial sow populations...

Long-term non-progressors (LTNP) and elite controllers (EC) represent spontaneous natural models of efficient HIV-1 response in the absence of treatment. The main purposes of this work are to describe the miRNome of HIV-1 infected patients with different extreme phenotypes and identify potentially altered pathways regulated by differentially expressed (DE) miRNAs. The miRNomes from peripheral blood mononuclear cells (PBMCs) of dual phenotype EC-LTNP or LTNP with detectable viremia and HIV-infected patients with typical progression before and after treatment, were obtained through miRNA-Seq and compared among them...