scholarly journals Prolonged Suppression of Human Immunodeficiency Virus Type 1 (HIV‐1) Viremia in Persons with Advanced Disease Results in Enhancement of CD4 T Cell Reactivity to Microbial Antigens but Not to HIV‐1 Antigens

1999 ◽  
Vol 179 (2) ◽  
pp. 329-336 ◽  
Author(s):  
Charles R. Rinaldo, Jr. ◽  
James M. Liebmann ◽  
Xiao‐Li Huang ◽  
Zheng Fan ◽  
Qasim Al‐Shboul ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Advanced Disease ◽  
Cd4 T Cell ◽  
Cell Reactivity ◽  
Immunodeficiency Virus ◽  
T Cell Reactivity ◽  
Hiv 1

scholarly journals Entry and Transcription as Key Determinants of Differences in CD4 T-Cell Permissiveness to Human Immunodeficiency Virus Type 1 Infection

2004 ◽  
Vol 78 (19) ◽  
pp. 10747-10754 ◽  
Author(s):  
Angela Ciuffi ◽  
Gabriela Bleiber ◽  
Miguel Muñoz ◽  
Raquel Martinez ◽  
Corinne Loeuillet ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Virus Production ◽  
Cd4 T Cell ◽  
Total Variance ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Isolated primary human cells from different donors vary in their permissiveness—the ability of cells to be infected and sustain the replication of human immunodeficiency virus type 1 (HIV-1). We used replicating HIV-1 and single-cycle lentivirus vectors in a population approach to identify polymorphic steps during viral replication. We found that phytohemagglutinin-stimulated CD4+ CD45RO+ CD57− T cells from healthy blood donors (n = 128) exhibited a 5.2-log-unit range in virus production. For 20 selected donors representing the spectrum of CD4 T-cell permissiveness, we could attribute up to 42% of the total variance in virus production to entry factors and 48% to postentry steps. Efficacy at key intracellular steps of the replicative cycle (reverse transcription, integration, transcription and splicing, translation, and budding and release) varied from 0.71 to 1.45 log units among donors. However, interindividual differences in transcription efficiency alone accounted for 64 to 83% of the total variance in virus production that was attributable to postentry factors. While vesicular stomatitis virus G protein-mediated fusion was more efficacious than CCR5/CD4 entry, the latter resulted in greater transcriptional activity per proviral copy. The phenotype of provirus transcription was stable over time, indicating that it represents a genetic trait.

scholarly journals The Heptad Repeat 2 Domain Is a Major Determinant for Enhanced Human Immunodeficiency Virus Type 1 (HIV-1) Fusion and Pathogenicity of a Highly Pathogenic HIV-1 Env

2009 ◽  
Vol 83 (22) ◽  
pp. 11715-11725 ◽  
Author(s):  
Vijay Sivaraman ◽  
Liguo Zhang ◽  
Eric G. Meissner ◽  
Jerry L. Jeffrey ◽  
Lishan Su
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Cd4 T Cell ◽  
Heptad Repeat ◽  
Fusion Activity ◽  
Highly Pathogenic ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-mediated depletion of CD4+ lymphocytes in an infected individual is the hallmark of progression to AIDS. However, the mechanism for this depletion remains unclear. To identify mechanisms of HIV-1-mediated CD4 T-cell death, two similar viral isolates obtained from a rapid progressor patient with significantly different pathogenic phenotypes were studied. One isolate (R3A) demonstrates enhanced pathogenesis in both in vivo models and relevant ex vivo lymphoid organ model systems compared to another isolate, R3B. The pathogenic determinants were previously mapped to the V5-gp41 envelope region, correlating functionally with enhanced fusion activity and elevated CXCR4 binding affinity. To further elucidate specific differences between R3A and R3B within the V5-gp41 domains that enhance CD4 depletion, R3A-R3B chimeras to study the V5-gp41 region were developed. Our data demonstrate that six residues in the ectodomain of R3A provide the major determinant for both enhanced Env-cell fusion and pathogenicity. Furthermore, three amino acid differences in the heptad repeat 2 (HR-2) domain of R3A determined its fusion activity and significantly elevated its pathogenic activity. The chimeric viruses with enhanced fusion activity, but not elevated CXCR4 affinity, correlated with high pathogenicity in the thymus organ. We conclude that the functional domain of a highly pathogenic HIV-1 Env is determined by mutations in the HR-2 region that contribute to enhanced fusion and CD4 T-cell depletion.

scholarly journals Levels of Soluble CD40 Ligand (CD154) in Serum Are Increased in Human Immunodeficiency Virus Type 1-Infected Patients and Correlate with CD4+ T-Cell Counts

2002 ◽  
Vol 9 (3) ◽  
pp. 558-561 ◽  
Author(s):  
Nikolaos V. Sipsas ◽  
Petros P. Sfikakis ◽  
Athanasios Kontos ◽  
Theodore Kordossis
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Cd40 Ligand ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT CD40 ligand (CD40L or CD154) is a costimulatory molecule expressed mainly on activated CD4+ T cells. Concentrations of the soluble form of CD40L (sCD40L) in serum were determined for a cohort of 77 human immunodeficiency virus type 1 (HIV-1)-infected patients before and after initiation of highly active antiretroviral treatment (HAART) by a quantitative enzyme-linked immunosorbent assay. Circulating sCD40L levels were higher by twofold in untreated patients than in healthy controls (means ± standard deviations [SD]: 1.41 ± 1.48 versus 0.69 ± 0.59 ng/ml; P < 0.001). HIV-1-infected patients classified as CD4 T-cell category 1 had significantly higher sCD40L levels than patients classified as CD4 categories 2 and 3 (mean ± SD: 2.08 ± 1.46 ng/ml versus 1.57 ± 1.58 [category 2] and 0.94 ± 1.25 ng/ml [category 3]; P = 0.046), while no correlation with clinical categories A, B, and C was found. Individual serum sCD40L levels correlated with CD4+ T-cell counts (P = 0.039) but not with viral load, gamma globulin levels, or acute-inflammatory-response markers. After 8 to 12 months of HAART, a further threefold increase of serum sCD40L levels, which paralleled the increase of CD4+ T-cell counts, was observed. These novel findings suggest that sCD40L measurement in HIV-1-infected patients could serve as a new surrogate marker useful in the assessment of treatment efficacy, especially in settings where well-equipped laboratories and funding required for CD4+ T-cell count and viral load measurements are not available.

Once-daily Doravirine in Human Immunodeficiency Virus Type 1–Infected, Antiretroviral-naive Adults: An Integrated Efficacy Analysis

2019 ◽  
Vol 70 (7) ◽  
pp. 1344-1352 ◽  
Author(s):  
Chloe Orkin ◽  
Jean-Michel Molina ◽  
Johan Lombaard ◽  
Edwin DeJesus ◽  
Anthony Rodgers ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Count ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cd4 T Cell ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Cd4 T Cell Count

AbstractBackgroundDoravirine (DOR) demonstrated noninferior efficacy to darunavir plus ritonavir (DRV+r) and efavirenz (EFV) in 2 ongoing phase 3 trials: DRIVE-FORWARD (NCT02275780) and DRIVE-AHEAD (NCT02403674).MethodsThis prespecified analysis pooled efficacy data through the first 48 weeks of DRIVE-FORWARD and DRIVE-AHEAD from the DOR groups (DOR/lamivudine [3TC]/tenofovir disoproxil fumarate [TDF] or DOR [100 mg daily] with emtricitabine [FTC]/TDF or abacavir [ABC]/3TC [n = 747]) compared with DRV+r (800/100 mg daily) with FTC/TDF or ABC/3TC (n = 383) or EFV/FTC/TDF (600/200/300 mg daily; n = 364). Efficacy assessments included the proportion of participants with human immunodeficiency virus type 1 (HIV-1) RNA &lt;50 copies/mL and change in CD4+ T-cell count.ResultsAt week 48, DOR demonstrated noninferior efficacy to DRV+r and EFV, with 84.1% of DOR-treated participants achieving HIV-1 RNA &lt;50 copies/mL compared with 79.9% of the DRV+r and 80.8% of the EFV groups. Results were similar across demographic/prognostic subpopulations, including baseline plasma HIV-1 RNA, gender, race, and HIV-1 subtype. Mean increases from baseline in CD4+ T-cell count through 48 weeks were 195.5 cells/mm3 for DOR, 185.6 cells/mm3 for DRV+r, and 188.4 cells/mm3 for EFV/FTC/TDF.ConclusionsDOR, as a single entity (in combination with other antiretroviral agents) and as a fixed-dose combination (DOR/3TC/TDF), demonstrated noninferior efficacy to DRV+r and EFV as assessed by the proportion of HIV-1-infected, treatment-naive adults with HIV-1 RNA &lt;50 copies/mL.Clinical Trials RegistrationNCT02275780 and NCT02403674.

scholarly journals Multiple T-Cell Responses to Human Immunodeficiency Virus Type 1 Are Enhanced by Dendritic Cells

2009 ◽  
Vol 16 (10) ◽  
pp. 1504-1516 ◽  
Author(s):  
Xiao-Li Huang ◽  
Zheng Fan ◽  
LuAnn Borowski ◽  
Charles R. Rinaldo
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Cell Proliferation ◽  
Cell Reactivity ◽  
Cell Functions ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
T Cell Reactivity ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-specific T-cell reactivity has been related to protection from disease progression. Optimal T-cell reactivity to HIV-1 presumably requires antigen processing and presentation by professional antigen-presenting cells, particularly dendritic cells (DC). Here we examined whether multiple HIV-1-specific T-cell functions are enhanced by stimulation with HIV-1 peptide-loaded DC derived from HIV-1-infected subjects on antiretroviral therapy. We first found that mature DC increased the number of gamma interferon (IFN-γ)-producing T cells detected by enzyme-linked immunospot assay to overlapping 15-mer peptides of HIV-1 Gag and Nef, compared to stimulation with peptide-loaded, immature DC or to peptides without DC. IFN-γ production was lower in response to large pools of the Gag and Nef peptides, regardless of presentation by DC. We further observed that HIV-1 peptide-loaded, mature DC stimulated greater CD8+ and CD4+ T-cell proliferation than did the peptides without DC and that T-cell proliferation was lower in response to larger pools of the peptides. The lower T-cell IFN-γ and proliferation responses to the larger peptide pools were related to lower T-cell viability. Finally, the number of polyfunctional CD8+ and CD4+ T cells stimulated by HIV-1 peptide-loaded, mature DC, defined as positive by intracellular staining for more than one immune mediator (IFN-γ, interleukin 2, tumor necrosis factor alpha, macrophage inhibitory protein 1β, or CD107a), was greater than that stimulated by the peptides alone. These results indicate that DC can enhance multiple types of HIV-1-specific T-cell functions.

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