scholarly journals Undetectable Anti-HBs Antibodies: Need of a Booster Dose for HIV-1-Infected Individuals

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1484
Author(s):  
Yonas Bekele ◽  
Jay A. Berzofsky ◽  
Francesca Chiodi

HBV vaccination effectively prevents HBV transmission and the development of liver cancer. Disease progression and liver-related complications are more common in HIV-1/HBV co-infected than HBV mono-infected individuals. A considerable body of literature, which will be reviewed here, indicates that response to HBV vaccine is suboptimal in HIV-1-infected individuals and that the poor maintenance of protective immunity to HBV vaccines in these individuals is an important medical issue. Several factors affect HBV vaccine response during HIV-1 infection including CD4+ T cell counts, B cell response, vaccine formulation, schedules, and timing of antiretroviral therapy (ART). The initial response to HBV vaccination also plays a critical role in the sustainability of antibody responses in both HIV-1-infected and uninfected vaccinees. Thus, regular follow-up for antibody titer and a booster dose is warranted to prevent HBV transmission in HIV-1 infected people.

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Peng Dai ◽  
Feng-Ying Wu ◽  
Cheng Cui ◽  
Xue-Jiao Liao ◽  
Yan-Mei Jiao ◽  
...  

Chronic HIV-1 infection is associated with persistent inflammation, which contributes to disease progression. Platelet-T cell aggregates play a critical role in maintaining inflammation. However, the phenotypic characteristics and clinical significance of platelet-CD4+ T cell aggregates remain unclear in different HIV-infected populations. In this study, we quantified and characterized platelet-CD4+ T cell aggregates in the peripheral blood of treatment-naïve HIV-1-infected individuals (TNs), immunological responders to antiretroviral therapy (IRs), immunological non-responders to antiretroviral therapy (INRs), and healthy controls (HCs). Flow cytometry analysis and immunofluorescence microscopy showed increased platelet-CD4+ T cell aggregate formation in TNs compared to HCs during HIV-1 infection. However, the frequencies of platelet-CD4+ T cell aggregates decreased in IRs compared to TNs, but not in INRs, which have shown severe immunological dysfunction. Platelet-CD4+ T cell aggregate frequencies were positively correlated with HIV-1 viral load but negatively correlated with CD4+ T cell counts and CD4/CD8 ratios. Furthermore, we observed a higher expression of CD45RO, HIV co-receptors, HIV activation/exhaustion markers in platelet-CD4+ T cell aggregates, which was associated with HIV-1 permissiveness. High levels of caspase-1 and caspase-3, and low levels of Bcl-2 in platelet-CD4+ T cell aggregates imply the potential role in CD4+ T cell loss during HIV-1 infection. Furthermore, platelet-CD4+ T cell aggregates contained more HIV-1 gag viral protein and HIV-1 DNA than their platelet-free CD4+ T cell counterparts. The platelet-CD4+ T cell aggregate levels were positively correlated with plasma sCD163 and sCD14 levels. Our findings demonstrate that platelet-CD4+ T cell aggregate formation has typical characteristics of HIV-1 permissiveness and is related to immune activation during HIV-1 infection.


2018 ◽  
Author(s):  
Inés Herrero-Fernéndez ◽  
Isaac Rosado-Sánchez ◽  
Miguel Genebat ◽  
Laura Tarancón-Díez ◽  
María Mar Rodríguez-Méndez ◽  
...  

ABSTRACTIntroductionWe previously found that a maraviroc-containing combined antiretroviral therapy (MVC-cART) was associated with a better response to the Hepatitis B Virus (HBV) vaccine in HIV-infected subjects younger than 50 years old. We aimed here to extend our previous analysis including immunological parameters related to inflammation, T-cell and dendritic cell (DC) subsets phenotype and to explore the impact of MVC-cART on these parameters.MethodsWe analyzed baseline samples of vaccinated subjects under 50 years old (n=41). We characterized CD4 T-cells according to the distribution of their maturational subsets and the expression of activation, senescence and prone-to-apoptosis markers; we also quantified Treg-cells and main DC subsets. Linear regressions were performed to determine the impact of these variables on the magnitude of vaccine response. Binary logistic regressions were explored to analyze the impact of MVC-cART on immunological parameters. Correlations with the time of MVC exposure were also explored.ResultsMVC-cART remained independently associated with HBV-vaccine responsiveness even after adjusting by immunological variables. The %CD4+CD25hiFoxP3+ki67+ and %pDCs were also independently associated. Moreover, HIV-infected subjects on MVC-containing therapy prior to vaccination showed lower inflammatory levels, activated CD4 T-cells and frequency of Treg cells and higher frequency of recent thymic emigrants.ConclusionTreg-cell levels negatively impacted the HBV-vaccine response, whereas higher pDCs levels and a MVC-cART prior to vaccination were associated with better responsiveness. These factors together with the improved phenotypic CD4 T-cell profile and the lower inflammatory levels found in subjects with a MVC-cART prior HBV vaccination could contribute to their enhanced vaccine response.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lianwei Ma ◽  
Hui Zhang ◽  
Yue Zhang ◽  
Hailong Li ◽  
Minghui An ◽  
...  

Abstract Background Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. Methods 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. Results A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. Conclusions This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.


Intervirology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Mohammad Reza Jabbari ◽  
Hoorieh Soleimanjahi ◽  
Somayeh Shatizadeh Malekshahi ◽  
Mohammad Gholami ◽  
Leila Sadeghi ◽  
...  

<b><i>Objectives:</i></b> The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count &#x3c;100 cells/mm<sup>3</sup> and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. <b><i>Methods:</i></b> This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count &#x3c;100 cells/mm<sup>3</sup>, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). <b><i>Results:</i></b> Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (<i>p</i> value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (<i>p</i> &#x3c; 0.02). <b><i>Conclusions:</i></b> We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count &#x3c;100 mm<sup>3</sup>/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.


Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 852
Author(s):  
Ashley Lauren Bennett ◽  
Rory Henderson

The HIV-1 envelope glycoprotein (Env) mediates host cell fusion and is the primary target for HIV-1 vaccine design. The Env undergoes a series of functionally important conformational rearrangements upon engagement of its host cell receptor, CD4. As the sole target for broadly neutralizing antibodies, our understanding of these transitions plays a critical role in vaccine immunogen design. Here, we review available experimental data interrogating the HIV-1 Env conformation and detail computational efforts aimed at delineating the series of conformational changes connecting these rearrangements. These studies have provided a structural mapping of prefusion closed, open, and transition intermediate structures, the allosteric elements controlling rearrangements, and state-to-state transition dynamics. The combination of these investigations and innovations in molecular modeling set the stage for advanced studies examining rearrangements at greater spatial and temporal resolution.


Author(s):  
Claes Martin ◽  
Jan Albert ◽  
Per Hansson ◽  
PehrOlov Pehrsson ◽  
Hans Link ◽  
...  

The Lancet ◽  
2000 ◽  
Vol 356 (9239) ◽  
pp. 1412-1413 ◽  
Author(s):  
Esteban Martínez ◽  
Luis Bianchi ◽  
Miguel Angel García-Viejo ◽  
Concepción Bru ◽  
José M Gatell

2012 ◽  
Vol 86 (18) ◽  
pp. 9802-9816 ◽  
Author(s):  
Melissa M. Norström ◽  
Marcus Buggert ◽  
Johanna Tauriainen ◽  
Wendy Hartogensis ◽  
Mattia C. Prosperi ◽  
...  

HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although rates can vary within this group. Underlying mechanisms are not fully understood but likely involve both immunological and virological dynamics. The present study investigated HIV-1in vivoevolution and epitope-specific CD8+T cell responses in six HLA-B*5701 patients who had not received antiretroviral treatment, monitored from early infection for up to 7 years. The subjects were classified as high-risk progressors (HRPs) or low-risk progressors (LRPs) based on baseline CD4+T cell counts. Dynamics of HIV-1 Gag p24 evolution and multifunctional CD8+T cell responses were evaluated by high-resolution phylogenetic analysis and polychromatic flow cytometry, respectively. In all subjects, substitutions occurred more frequently in flanking regions than in HLA-B*5701-restricted epitopes. In LRPs, p24 sequence diversity was significantly lower; sequences exhibited a higher degree of homoplasy and more constrained mutational patterns than HRPs. The HIV-1 intrahost evolutionary rate was also lower in LRPs and followed a strict molecular clock, suggesting neutral genetic drift rather than positive selection. Additionally, polyfunctional CD8+T cell responses, particularly to TW10 and QW9 epitopes, were more robust in LRPs, who also showed significantly higher interleukin-2 (IL-2) production in early infection. Overall, the findings indicate that HLA-B*5701 patients with higher CD4 counts at baseline have a lower risk of HIV-1 disease progression because of the interplay between specific HLA-linked immune responses and the rate and mode of viral evolution. The study highlights the power of a multidisciplinary approach, integrating high-resolution evolutionary and immunological data, to understand mechanisms underlying HIV-1 pathogenesis.


1995 ◽  
Vol 108 (8) ◽  
pp. 2811-2823 ◽  
Author(s):  
M. Dundr ◽  
G.H. Leno ◽  
M.L. Hammarskjold ◽  
D. Rekosh ◽  
C. Helga-Maria ◽  
...  

The human immunodeficiency virus 1 (HIV-1) Rev transactivator protein plays a critical role in the regulation of expression of structural proteins by controlling the pathway of mRNA transport. The Rev protein is located predominantly in the nucleoli of HIV-1 infected or Rev-expressing cells. Previous studies demonstrated that the Rev protein forms a specific complex in vitro with protein B23 which is suggested to be a nucleolar receptor and/or carrier for the Rev protein. To study the role of the nucleolus and nucleolar proteins in Rev function, transfected COS-7 or transformed CMT3 cells expressing the Rev protein were examined for subcellular locations of Rev and other proteins using indirect immunofluorescence and immunoelectron microscopy. One day after transfection the Rev protein was found in most cells only in the nucleolar dense fibrillar and granular components where it colocalized with protein B23. These were designated class 1 cells. In a second class of cells Rev and B23 accumulated in the nucleoplasm as well as in nucleoli. Treatment of class 1 cells with actinomycin D (AMD) under conditions that blocked only RNA polymerase I transcription caused Rev to completely redistribute from nucleoli to the cytoplasm. Simultaneously, protein B23 was partially released from nucleoli, mostly into the nucleoplasm, with detectable amounts in the cytoplasm. In cells recovering from AMD treatment in the presence of cycloheximide Rev and B23 showed coincident relocation to nucleoli. Class 2 cells were resistant to AMD-induced Rev redistribution. Selective inhibition of RNA polymerase II transcription by alpha-amanitin or by DRB did not cause Rev to be released into the cytoplasm suggesting that active preribosomal RNA transcription is required for the nucleolar location of Rev. However, treatment with either of the latter two drugs at higher doses and for longer times caused partial disruption of nucleoli accompanied by translocation of the Rev protein to the cytoplasm. These results suggest that the nucleolar location of Rev depends on continuous preribosomal RNA transcription and a substantially intact nucleolar structure.


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