Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus Infections

Stacey, Andrea; Norris, Philip J.; Li, Qin; Haygreen, E; Taylor, E. G.; Heitman, John W.; Lebedeva, Mila; deCamp, Allan C.; Li, Dongfeng; Grove, Douglas I.; Self, Steven G.; Borrow, Persephone

doi:10.1128/jvi.01844-08

Cited by 647 publications

(705 citation statements)

References 47 publications

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“…2 Levels of TNF-a, IL-6, hs-CRP, and other proinflammatory cytokines are associated with HIV-1 viral load and may predict disease progression, as well as correlate with a higher risk of CVD and all-cause mortality. [42][43][44][45] Our findings corroborate another recent analysis, which reported that only d-dimer, and not IL-6 or hs-CRP, is reduced over the short term in those initiating ARV therapy. 46 Additionally, the reductions in LPS observed here are similar in magnitude to those seen in a previous study 47 ; the similar reductions in the DRV/r and ATV/r arms suggest that these ARV agents do not result in differential levels of LPS, a trigger of persistent immune activation in ARV-treated individuals.…”

Section: Discussionsupporting

confidence: 82%

“…39 Subjects infected with HIV-1 have increased levels of hs-CRP, TNF alpha (TNF-a), IL-6, d-dimer, and other biomarkers compared with HIV-negative subjects. 2,[40][41][42] These elevations in biomarkers persist even after virologic suppression, likely due to HIV-induced activation of inflammation and coagulation pathways. 2 Levels of TNF-a, IL-6, hs-CRP, and other proinflammatory cytokines are associated with HIV-1 viral load and may predict disease progression, as well as correlate with a higher risk of CVD and all-cause mortality.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Aberg

Tebas

Overton

et al. 2012

AIDS Research and Human Retroviruses

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We assessed metabolic changes for darunavir/ritonavir (DRV/r) once daily (qd) versus atazanavir/ritonavir (ATV/r) qd with fixed-dose tenofovir/emtricitabine. This was a phase 4, multicenter, open-label, randomized exploratory study. Treatment-naive, HIV-1-infected adults received DRV/r 800/100 mg qd or ATV/r 300/ 100 mg qd, both with emtricitabine/tenofovir 200/300 mg qd. Primary end point: change in triglyceride levels from baseline to week 12. Secondary end points: week 12 and week 48 changes in lipid parameters, insulin sensitivity, inflammatory/coagulation/bacterial translocation biomarkers, viral load, CD4 + cell count, and week 48 changes in adipose tissue distribution and subjects' perceptions of body changes. In the DRV/r arm, 32/34 and 29/34 subjects completed weeks 12 and 48, respectively; in the ATV/r arm, 30/31 and 25/31 subjects completed weeks 12 and 48, respectively. Small changes in lipid parameters from baseline to weeks 12 and 48 were observed in both arms. Differences were noted between arms in mean changes in total cholesterol (DRV/r, 20.3 mg/dl; ATV/r, 4.6 mg/dl) and apolipoprotein A1 (DRV/r, 10.7 mg/dl; ATV/r, -0.7 mg/dl) at week 12. At week 48, no clinically relevant differences between arms were noted for changes in any lipid parameter, fasting glucose, or insulin sensitivity. Biomarkers generally decreased and efficacy parameters improved in both arms over 48 weeks. Changes in adipose tissue were small and comparable between arms. Subjects' perceptions of body changes generally improved in both study arms. This first pilot comparison in HIV-1-infected subjects suggests that DRV/r has a metabolic profile similar to ATV/r over 48 weeks of treatment. Further randomized studies are warranted.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Aberg

Tebas

Overton

et al. 2012

AIDS Research and Human Retroviruses

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“…Stacey et al analysed the changes in the cytokine profiles during the "eclipse" phase of acute HIV-1 infection by analysing samples collected in 2-5 day periods [26]. Initial increase in IFN-α, IL-15, TNF-α, IP-10 and MCP-1 concentrations was followed by a rise in IL-6, IL-8, IL-10, IL-18 and IFN-γ whereas the increase in IL-4, IL-5, IL-12 and IL-22 concentrations was observed later.…”

Section: Discussionmentioning

confidence: 99%

The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection

Gorenec

Lepej

Grgic

et al. 2016

Microbial Pathogenesis

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“…It is possible that trafficking of the negative regulatory factor (Nef) protein from HIV‐1‐infected macrophages to B cells may alter class switching and germinal center (GC) responses,58 but dysfunction is also likely driven by the early cytokine storm59 and ongoing immune dysfunction caused by HIV‐1 infection of T cells. B‐cell dysregulation is evidenced by the delayed antibody response in acute HIV‐1 infection,41 an increase in the proportion of activated memory B cells and exhausted B cells, non‐specific plasmablast activation (leading to polyclonal immunoglobulin production), and a decline in the frequency of long‐lived plasma cells 42, 60, 61, 62, 63.…”

Section: Development Of Broadly Neutralizing Antibodies In Hiv‐1 Infementioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

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SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

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Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus Infections

Abstract: Characterization of the immune responses induced in the initial stages of human immunodeficiency virus type 1 (HIV-1

Cited by 647 publications

References 47 publications

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

Metabolic Effects of Darunavir/Ritonavir Versus Atazanavir/Ritonavir in Treatment-Naive, HIV Type 1-Infected Subjects over 48 Weeks

The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

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