Immunological and epidemiological evaluation of EBV infections among HIV-1 infected individuals in Abakaliki, Nigeria supports the potential use of neutrophils as a marker of EBV in HIV disease progression and as useful markers of immune activation

2019 ◽  
Vol 41 (2) ◽  
pp. 158-170
Author(s):  
Iheanyi Omezuruike Okonko ◽  
Taiwo Salami Makinde ◽  
Blessing Jachinma Okonko ◽  
Ogbonnaya Ogbu
Keyword(s):  
Disease Progression ◽  
Immune Activation ◽  
Hiv Disease ◽  
Epidemiological Evaluation ◽  
Potential Use ◽  
Hiv 1

scholarly journals HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis

Blood ◽  
2011 ◽  
Vol 117 (19) ◽  
pp. 5142-5151 ◽  
Author(s):  
Delphine Sauce ◽  
Martin Larsen ◽  
Solène Fastenackels ◽  
Michèle Pauchard ◽  
Hocine Ait-Mohand ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Progression ◽  
Immune Activation ◽  
The Elderly ◽  
Cd4 T Cell ◽  
Large Set ◽  
Hiv Disease ◽  
Hiv Replication ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract The mechanisms of CD4+ T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4+ T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4+ T-cell levels probably depends primarily on the capacity to renew depleted lymphocytes, that is, the lymphopoiesis. We performed here a comprehensive study of quantitative and qualitative attributes of CD34+ hematopoietic progenitor cells directly from the blood of a large set of HIV-infected persons compared with uninfected donors, in particular the elderly. Our analyses underline a marked impairment of primary immune resources with the failure to maintain adequate lymphocyte counts. Systemic immune activation emerges as a major correlate of altered lymphopoiesis, which can be partially reversed with prolonged antiretroviral therapy. Importantly, HIV disease progression despite elite control of HIV replication or virologic success on antiretroviral treatment is associated with persistent damage to the lymphopoietic system or exhaustion of lymphopoiesis. These findings highlight the importance of primary hematopoietic resources in HIV pathogenesis and the response to antiretroviral treatments.

scholarly journals Selenium Status Is Associated with Accelerated HIV Disease Progression among HIV-1–Infected Pregnant Women in Tanzania

2004 ◽  
Vol 134 (10) ◽  
pp. 2556-2560 ◽  
Author(s):  
Roland Kupka ◽  
Gernard I. Msamanga ◽  
Donna Spiegelman ◽  
Steve Morris ◽  
Ferdinand Mugusi ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Disease Progression ◽  
Hiv Disease ◽  
Selenium Status ◽  
Hiv 1

IL-7Rα expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation

2006 ◽  
Vol 36 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Sandra A. Koesters ◽  
Judie B. Alimonti ◽  
Charles Wachihi ◽  
Lucy Matu ◽  
Omu Anzala ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Disease Progression ◽  
Immune Activation ◽  
Hiv Disease

scholarly journals Effect of aspirin on HIV disease progression among HIV-infected individuals initiating antiretroviral therapy: study protocol for a randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e049330
Author(s):  
Tosi Mwakyandile ◽  
Grace Shayo ◽  
Sabina Mugusi ◽  
Bruno Sunguya ◽  
Philip Sasi ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Disease Progression ◽  
Immune Activation ◽  
Controlled Trial ◽  
Cd4 Count ◽  
People Living With Hiv ◽  
Hiv Disease ◽  
Hiv Viral Load ◽  
Double Blind ◽  
Randomised Controlled

IntroductionAn increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression.Methods and analysisA single-centre phase IIA double-blind, parallel-group randomised controlled trial intends to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants are randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of <50 copies/mL by 8, 12 and 24 weeks. Secondary outcomes include proportions of participants with HVL of >1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes.Ethics and disseminationEthical approval has been obtained from institutional and national ethics review committees. Findings will be submitted to peer-reviewed journals and presented in scientific conferences.Trial registration numberPACTR202003522049711.

Serum HIV–1 RNA Levels Compared to Soluble Markers of Immune Activation to Predict Disease Progression in HIV–1–Infected Individuals

1998 ◽  
Vol 116 (3) ◽  
pp. 228-239 ◽  
Author(s):  
Robert Zangerle ◽  
Sabine Steinhuber ◽  
Mario Sarcletti ◽  
Manfred P. Dierich ◽  
Helmut Wachter ◽  
...  
Keyword(s):  
Disease Progression ◽  
Immune Activation ◽  
Hiv 1 ◽  
Predict Disease Progression ◽  
Rna Levels

scholarly journals Replicative fitness of transmitted HIV-1 drives acute immune activation, proviral load in memory CD4+ T cells, and disease progression

2015 ◽  
Vol 112 (12) ◽  
pp. E1480-E1489 ◽  
Author(s):  
Daniel T. Claiborne ◽  
Jessica L. Prince ◽  
Eileen Scully ◽  
Gladys Macharia ◽  
Luca Micci ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Progression ◽  
T Cell Activation ◽  
Immune Activation ◽  
Cell Activation ◽  
Viral Reservoir ◽  
Replicative Fitness ◽  
Cell Decline ◽  
Protective Genes ◽  
Hiv 1

HIV-1 infection is characterized by varying degrees of chronic immune activation and disruption of T-cell homeostasis, which impact the rate of disease progression. A deeper understanding of the factors that influence HIV-1–induced immunopathology and subsequent CD4+ T-cell decline is critical to strategies aimed at controlling or eliminating the virus. In an analysis of 127 acutely infected Zambians, we demonstrate a dramatic and early impact of viral replicative capacity (vRC) on HIV-1 immunopathogenesis that is independent of viral load (VL). Individuals infected with high-RC viruses exhibit a distinct inflammatory cytokine profile as well as significantly elevated T-cell activation, proliferation, and CD8+ T-cell exhaustion, during the earliest months of infection. Moreover, the vRC of the transmitted virus is positively correlated with the magnitude of viral burden in naive and central memory CD4+ T-cell populations, raising the possibility that transmitted viral phenotypes may influence the size of the initial latent viral reservoir. Taken together, these findings support an unprecedented role for the replicative fitness of the founder virus, independent of host protective genes and VL, in influencing multiple facets of HIV-1–related immunopathology, and that a greater focus on this parameter could provide novel approaches to clinical interventions.

scholarly journals Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection

2018 ◽  
Vol 92 (19) ◽  
Author(s):  
Doty B. A. Ojwach ◽  
Daniel MacMillan ◽  
Tarylee Reddy ◽  
Vladimir Novitsky ◽  
Zabrina L. Brumme ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Disease Progression ◽  
Chronic Infection ◽  
Hiv Disease ◽  
Subtype C ◽  
Recombinant Viruses ◽  
Immune Mediated ◽  
Hiv 1

ABSTRACT CD8+ T cell-mediated escape mutations in Gag can reduce HIV-1 replication capacity (RC) and alter disease progression, but less is known about immune-mediated attenuation in other HIV-1 proteins. We generated 487 recombinant viruses encoding RT-integrase from individuals with chronic (n = 406) and recent (n = 81) HIV-1 subtype C infection and measured their in vitro RC using a green fluorescent protein (GFP) reporter T cell assay. In recently infected individuals, reverse transcriptase (RT)-integrase-driven RC correlated significantly with viral load set point (r = 0.25; P = 0.03) and CD4+ T cell decline (P = 0.013). Moreover, significant associations between RT integrase-driven RC and viral load (r = 0.28; P < 0.0001) and CD4+ T cell count (r = −0.29; P < 0.0001) remained in chronic infection. In early HIV infection, host expression of the protective HLA-B*81 allele was associated with lower RC (P = 0.05), as was expression of HLA-B*07 (P = 0.02), suggesting early immune-driven attenuation of RT-integrase by these alleles. In chronic infection, HLA-A*30:09 (in linkage disequilibrium with HLA-B*81) was significantly associated with lower RC (P = 0.05), and all 6 HLA-B alleles with the lowest RC measurements represented protective alleles, consistent with long-term effects of host immune pressures on lowering RT-integrase RC. The polymorphisms V241I, I257V, P272K, and E297K in reverse transcriptase and I201V in integrase, all relatively uncommon polymorphisms occurring in or adjacent to optimally described HLA-restricted cytotoxic T-lymphocyte epitopes, were associated with reduced RC. Together, our data suggest that RT-integrase-driven RC is clinically relevant and provide evidence that immune-driven selection of mutations in RT-integrase can compromise RC. IMPORTANCE Identification of viral mutations that compromise HIV's ability to replicate may aid rational vaccine design. However, while certain escape mutations in Gag have been shown to reduce HIV replication and influence clinical progression, less is known about the consequences of mutations that naturally arise in other HIV proteins. Pol is a highly conserved protein, but the impact of Pol function on HIV disease progression is not well defined. Here, we generated recombinant viruses using the RT-integrase region of Pol derived from HIV-1C-infected individuals with recent and chronic infection and measured their ability to replicate in vitro. We demonstrate that RT-integrase-driven replication ability significantly impacts HIV disease progression. We further show evidence of immune-mediated attenuation in RT-integrase and identify specific polymorphisms in RT-integrase that significantly decrease HIV-1 replication ability, suggesting which Pol epitopes could be explored in vaccine development.

scholarly journals Plasma cytokine levels during acute HIV-1 infection predict HIV disease progression

AIDS ◽  
2010 ◽  
Vol 24 (6) ◽  
pp. 819-831 ◽  
Author(s):  
Lindi Roberts ◽  
Jo-Ann S Passmore ◽  
Carolyn Williamson ◽  
Francesca Little ◽  
Lisa M Bebell ◽  
...  
Keyword(s):  
Disease Progression ◽  
Hiv Disease ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Acute Hiv ◽  
Hiv 1

scholarly journals Meta-Analysis To Test the Association of HIV-1 nef Amino Acid Differences and Deletions with Disease Progression

2010 ◽  
Vol 84 (7) ◽  
pp. 3644-3653 ◽  
Author(s):  
Ravindra Pushker ◽  
Jean-Marc Jacqué ◽  
Denis C. Shields
Keyword(s):  
Amino Acid ◽  
Disease Progression ◽  
Meta Analysis ◽  
Amino Acid Replacement ◽  
Hiv Disease ◽  
Permutation Testing ◽  
Consensus Sequences ◽  
Subtype B ◽  
Hiv 1

ABSTRACT Previous relatively small studies have associated particular amino acid replacements and deletions in the HIV-1 nef gene with differences in the rate of HIV disease progression. We tested more rigorously whether particular nef amino acid differences and deletions are associated with HIV disease progression. Amino acid replacements and deletions in patients' consensus sequences were investigated for 153 progressor (P), 615 long-term nonprogressor (LTNP), and 2,311 unknown progressor sequences from 582 subtype B HIV-infected patients. LTNPs had more defective nefs (interrupted by frameshifts or stop codons), but on a per-patient basis there was no excess of LTNP patients with one or more defective nef sequences compared to the Ps (P = 0.47). The high frequency of amino acid replacement at residues S8, V10, I11, A15, V85, V133, N157, S163, V168, D174, R178, E182, and R188 in LTNPs was also seen in permuted datasets, implying that these are simply rapidly evolving residues. Permutation testing revealed that residues showing the greatest excess over expectation (A15, V85, N157, S163, V168, D174, R178, and R188) were not significant (P = 0.77). Exploratory analysis suggested a hypothetical excess of frameshifting in the regions 9SVIG and 118QGYF among LTNPs. The regions V10 and 152KVEEA of nef were commonly deleted in LTNPs. However, permutation testing indicated that none of the regions displayed significantly excessive deletion in LTNPs. In conclusion, meta-analysis of HIV-1 nef sequences provides no clear evidence of whether defective nef sequences or particular regions of the protein play a significant role in disease progression.

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