scholarly journals Plasma-derived HIV Nef+ exosomes persist in ACTG384 study participants despite successful virological suppression

2019 ◽  
Author(s):  
Andrea D. Raymond ◽  
Michelle J. Lang ◽  
Jane Chu ◽  
Tamika Campbell-Sims ◽  
Mahfuz Khan ◽  
...  
Keyword(s):  
Virological Suppression ◽  
Cell Recovery ◽  
Viral Loads ◽  
Aids Clinical Trial Group ◽  
Immunodeficiency Virus ◽  
Immunological Recovery ◽  
Clinical Associations ◽  
Study Participants ◽  
Cd4 Cell

AbstractHuman Immunodeficiency Virus (HIV) accessory protein Negative factor (Nef) is detected in the plasma of HIV+ individuals associated with exosomes. The role of Nef+ exosomes (exNef) in HIV pathogenesis is unknown. We perform a retrospective longitudinal analysis to determine correlative clinical associations of exNef plasma levels in ARV-treated HIV+ patients with or without immune recovery. exNef concentration in a subset of AIDS Clinical Trial Group (ACTG) 384 participants with successful virological suppression and with either high (Δ >100 CD4 cell recovery/High Immunological Responders (High-IR) or low (Δ ≤100 CD4 cell recovery/ Low Immunologic Responders (Low-IR) immunologic recovery was measured and compared for study weeks 48, 96, and 144. CD4 recovery showed a negative correlation with exNef at study week 144 (r = −0.3573, *p=.0366). Plasma exNef concentration in high IRs negatively correlated with naïve CD4 count and recovery (r = −0.3249, *p = 0. 0348 (High-IR); r =0.2981, *p= #0.0513 (Low-IR)). However, recovery of CD4 memory cells positively correlated with exNef (r =.4534, *p=.0358) in Low-IRs but not in High-IRs. Regimen A (Didanosine, Stavudine, Efavirenz) lowered exNef levels in IRs by 2-fold compared to other regimens. Nef+ exosomes persist in ART-treated HIV+ individuals despite undetectable viral loads, negatively correlates with naive and memory CD4 T cell restoration and may be associated with reduced immunological recovery. Taken together, these data suggest that exNef may represent a novel mechanism utilized by HIV to promote immune dysregulation.

scholarly journals Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals.

1996 ◽  
Vol 40 (11) ◽  
pp. 2664-2668 ◽  
Author(s):  
A M Been-Tiktak ◽  
I Williams ◽  
H M Vrehen ◽  
J Richens ◽  
D Aldam ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transcriptase Inhibitor ◽  
Viral Loads ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor ◽  
Cd4 Cell ◽  
Hiv 1

Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients.

scholarly journals Relative Dominance of Gag p24-Specific Cytotoxic T Lymphocytes Is Associated with Human Immunodeficiency Virus Control

2006 ◽  
Vol 80 (6) ◽  
pp. 3122-3125 ◽  
Author(s):  
Rosario Zuñiga ◽  
Aldo Lucchetti ◽  
Patricia Galvan ◽  
Shyla Sanchez ◽  
Carmen Sanchez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Vaccine Development ◽  
Cytotoxic T Lymphocyte ◽  
Dominant Role ◽  
The United States ◽  
Effective Control ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Ctl Responses

ABSTRACT Conflicting data on the role of total virus- and protein-specific cytotoxic-T-lymphocyte (CTL) responses in the control of human immunodeficiency virus (HIV) disease progression exist. We present data generated from a Peruvian cohort of untreated, clade B-infected subjects, demonstrating that the proportion of Gag-specific, and in particular p24-reactive, CTL responses among the total virus-specific CTL activity is associated with individuals' CD4 counts and viral loads. Analyses in a second cohort in the United States confirm these findings and point towards a dominant role of Gag-specific immunity in effective control of HIV infection, providing important guidance for HIV vaccine development.

scholarly journals Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703–positive individuals and their transmission recipients

2009 ◽  
Vol 206 (4) ◽  
pp. 909-921 ◽  
Author(s):  
Hayley Crawford ◽  
Wendy Lumm ◽  
Alasdair Leslie ◽  
Malinda Schaefer ◽  
Debrah Boeras ◽  
...  
Keyword(s):  
Viral Load ◽  
Hiv Replication ◽  
Rapid Disease Progression ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Ctl Responses

HLA-B*57 is the class I allele most consistently associated with control of human immunodeficiency virus (HIV) replication, which may be linked to the specific HIV peptides that this allele presents to cytotoxic T lymphocytes (CTLs), and the resulting efficacy of these cellular immune responses. In two HIV C clade–infected populations in South Africa and Zambia, we sought to elucidate the role of HLA-B*5703 in HIV disease outcome. HLA-B*5703–restricted CTL responses select for escape mutations in three Gag p24 epitopes, in a predictable order. We show that the accumulation of these mutations sequentially reduces viral replicative capacity in vitro. Despite this, in vivo data demonstrate that there is ultimately an increase in viral load concomitant with evasion of all three HLA-B*5703–restricted CTL responses. In HLA-B*5703–mismatched recipients, the previously described early benefit of transmitted HLA-B*5703–associated escape mutations is abrogated by the increase in viral load coincident with reversion. Rapid disease progression is observed in HLA-matched recipients to whom mutated virus is transmitted. These data demonstrate that, although costly escape from CTL responses can progressively attenuate the virus, high viral loads develop in the absence of adequate, continued CTL responses. These data underline the need for a CTL vaccine against multiple conserved epitopes.

scholarly journals Immunohistochemical Evaluation of T Cells in Oral Lesions from Human Immunodeficiency Virus-Positive Persons with Oropharyngeal Candidiasis

2003 ◽  
Vol 71 (2) ◽  
pp. 956-963 ◽  
Author(s):  
Tammy A. Myers ◽  
Janet E. Leigh ◽  
Alfredo R. Arribas ◽  
Shannon Hager ◽  
Rebecca Clark ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Host Defense ◽  
Oropharyngeal Candidiasis ◽  
Cell Numbers ◽  
Immunodeficiency Virus ◽  
Cd8 Cell ◽  
Immunohistochemical Studies ◽  
Cd4 Cell

ABSTRACT Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most frequent opportunistic fungal infection in human immunodeficiency virus (HIV)-positive persons. Although Th1-type CD4+ T cells are considered important for host defense against mucosal C. albicans infections, there is a paucity of information regarding the presence and/or role of T cells in OPC lesions. In pursuit of this, initial chromophore immunohistochemical studies showed a majority of CD8+ rather than CD4+ cells equally distributed throughout the buccal mucosa of OPC− persons (HIV− or HIV+), irrespective of blood CD4+ cell numbers. In contrast, CD8+ cells in lesions from HIV+ OPC+ persons were in significantly higher numbers and concentrated at the lamina propria-epithelium interface, a considerable distance from the Candida at the outer epithelium. Dual fluorescence and confocal microscopy confirmed that the majority of CD8+, but not CD4+, cells were T cells by the presence or absence, respectively, of CD3 on each cell type. These results suggest that CD8+ T cells may be important for oral host defense against OPC, especially when CD4 cell numbers are reduced, with a potential CD8 cell-specific dysfunction associated with susceptibility to OPC.

scholarly journals A tyrosine-based trafficking signal in the simian immunodeficiency virus envelope cytoplasmic domain is strongly selected for in pathogenic SIV infection

2021 ◽  
Author(s):  
Scott Lawrence ◽  
Samra E Elser ◽  
Workineh Torben ◽  
Robert V Blair ◽  
Bapi Pahar ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Cytoplasmic Domain ◽  
Open Reading Frames ◽  
Virus Envelope ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
First Time

The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-dependent trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting of Env. Despite extensive characterization, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which the Tyr-based signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY) replicates to high levels acutely in pigtail macaques (PTM) but is rapidly controlled. We previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion that encodes amino acids 734-736 (ΔQTH) and overlaps with the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected, which generated a new signal for polarized sorting but not endocytosis. This mutation by itself was sufficient to maintain high viral loads for several months when introduced into naive PTMs. These findings reveal, for the first time, strong selection pressure for Env endocytosis and, in particular, for polarized sorting during pathogenic SIV infection in vivo.

The significance of cytomegalovirus in children with pneumonia admitted for mechanical ventilation

2017 ◽  
Vol 21 (12) ◽  
pp. 1230-1236 ◽  
Author(s):  
P. M. Jeena ◽  
K. Govender ◽  
R. Parboosing ◽  
M. Adhikari
Keyword(s):  
Mechanical Ventilation ◽  
Lavage Fluid ◽  
Imaging Features ◽  
Cmv Infection ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
The Difference ◽  
Poor Outcomes ◽  
Dna Pcr

BACKGROUND: The pathogenic role of cytomegalovirus (CMV) among children with pneumonia is not clear.OBJECTIVES AND DESIGN: We describe the outcome of children on mechanical ventilation with ‘probable' CMV-related pneumonitis (CMV DNA polymerase chain reaction [PCR] positive as well as clinical and imaging features of CMV on ganciclovir) and children with pneumonia and CMV infection (CMV DNA PCR-positive without clinical and imaging features of CMV and not on ganciclovir therapy) at a paediatric intensive care unit in South Africa between 2011 and 2013. CMV viral loads were measured in non-bronchoscopic bronchoalveolar lavage fluid (NBBALF), plasma and whole-blood samples.RESULTS: Of the 97 children enrolled, 38 had CMV-related pneumonitis, 27 had pneumonia and CMV infection and 32 had pneumonia without CMV infection (negative CMV DNA PCR). Survival in the three groups was respectively 73.7% (P < 0.05), 92.6% (P < 0.05) and 88.0%. The difference in outcome could be accounted for by variance in the prevalence of human immunodeficiency virus (HIV) infection (respectively 60.5% and 29.6%, P < 0.05). A higher CMV viral load in NBBALF and plasma was seen in cases of CMV-related pneumonitis than in pneumonia with CMV infection: respectively log 5.20 vs. log 4.10 (P < 0.05) and 4.56 vs. 3.47 (P < 0.05).CONCLUSIONS: HIV-infected children on mechanical ventilation with CMV-related pneumonitis on ganciclovir have poor outcomes. Randomised placebo-controlled studies on ganciclovir are required.

You Are the One I Want to Communicate With!

2013 ◽  
Vol 44 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Sabrina Pierucci ◽  
Olivier Klein ◽  
Andrea Carnaghi
Keyword(s):  
Memory Bias ◽  
Shared Reality ◽  
Communication Partner ◽  
Shared Reality Theory ◽  
The One ◽  
Study Participants

This article investigates the role of relational motives in the saying-is-believing effect ( Higgins & Rholes, 1978 ). Building on shared reality theory, we expected this effect to be most likely when communicators were motivated to “get along” with the audience. In the current study, participants were asked to describe an ambiguous target to an audience who either liked or disliked the target. The audience had been previously evaluated as a desirable vs. undesirable communication partner. Only participants who communicated with a desirable audience tuned their messages to suit their audience’s attitude toward the target. In line with predictions, they also displayed an audience-congruent memory bias in later recall.

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