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

ABSTRACT: Both T-cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown.To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression.Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection.The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set point 12 months postinfection and time taken for CD4 cell counts to fall below 350 cells/microl were determined using multivariate and Cox proportional hazards regression.We found that the concentrations of five plasma cytokines, IL-12p40, IL-12p70, IFN-gamma, IL-7 and IL-15 in women with acute infection predicted 66% of the variation in viral load set point 12 months postinfection. IL-12p40, IL-12p70 and IFN-gamma were significantly associated with lower viral load, whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and granulocyte-macrophage colony-stimulating factor during acute infection were associated with maintenance of CD4 cell counts above 350 cells/microl, whereas IL-1alpha, eotaxin and IL-7 were associated with more rapid CD4 loss.A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women.

SUBMITTER: Roberts L

PROVIDER: S-EPMC3001189 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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

Roberts Lindi L Passmore Jo-Ann S JA Williamson Carolyn C Little Francesca F Bebell Lisa M LM Mlisana Koleka K Burgers Wendy A WA van Loggerenberg Francois F Walzl Gerhard G Djoba Siawaya Joel F JF Karim Quarraisha Abdool QA Karim Salim S Abdool SS

AIDS (London, England) 20100301 6

<h4>Background</h4>Both T-cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown.<h4>Objectives</h4>To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease prog ...[more]

PMID: 20224308

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Project description:T cell activation levels, viral load and CD4(+) T cell counts at early stages of HIV-1 infection are predictive of the rate of progression towards AIDS. We evaluated whether the inflammatory profile during primary HIV-1 infection is predictive of the virological and immunological set-points and of disease progression. We quantified 28 plasma proteins during acute and post-acute HIV-1 infection in individuals with known disease progression profiles. Forty-six untreated patients, enrolled during primary HIV-1 infection, were categorized into rapid progressors, progressors and slow progressors according to their spontaneous progression profile over 42 months of follow-up. Already during primary infection, rapid progressors showed a higher number of increased plasma proteins than progressors or slow progressors. The plasma levels of TGF-?1 and IL-18 in primary HIV-1 infection were both positively associated with T cell activation level at set-point (6 months after acute infection) and together able to predict 74% of the T cell activation variation at set-point. Plasma IP-10 was positively and negatively associated with, respectively, T cell activation and CD4(+) T cell counts at set-point and capable to predict 30% of the CD4(+) T cell count variation at set-point. Moreover, plasma IP-10 levels during primary infection were predictive of rapid progression. In primary infection, IP-10 was an even better predictor of rapid disease progression than viremia or CD4(+) T cell levels at this time point. The superior predictive capacity of IP-10 was confirmed in an independent group of 88 HIV-1 infected individuals. Altogether, this study shows that the inflammatory profile in primary HIV-1 infection is associated with T cell activation levels and CD4(+) T cell counts at set-point. Plasma IP-10 levels were of strong predictive value for rapid disease progression. The data suggest IP-10 being an earlier marker of disease progression than CD4(+) T cell counts or viremia levels.

Project description:The viral genotype has been shown to play an important role in HIV pathogenesis following transmission. However, the viral phenotypic properties that contribute to disease progression remain unclear. Most studies have been limited to the evaluation of Gag function in the context of a recombinant virus backbone. Using this approach, important biological information may be lost, making the evaluation of viruses obtained during acute infection, representing the transmitted virus, a more biologically relevant model. Here, we evaluate the roles of viral infectivity and the replication capacity of viruses from acute infection in disease progression in women who seroconverted in the CAPRISA 004 tenofovir microbicide trial. We show that viral replication capacity, but not viral infectivity, correlates with the set point viral load (Spearman r = 0.346; P = 0.045) and that replication capacity (hazard ratio [HR] = 4.52; P = 0.01) can predict CD4 decline independently of the viral load (HR = 2.9; P = 0.004) or protective HLA alleles (HR = 0.61; P = 0.36). We further demonstrate that Gag-Pro is not the main driver of this association, suggesting that additional properties of the transmitted virus play a role in disease progression. Finally, we find that although viruses from the tenofovir arm were 2-fold less infectious, they replicated at rates similar to those of viruses from the placebo arm. This indicates that the use of tenofovir gel did not select for viral variants with higher replication capacity. Overall, this study supports a strong influence of the replication capacity in acute infection on disease progression, potentially driven by interaction of multiple genes rather than a dominant role of the major structural gene gagIMPORTANCE HIV disease progression is known to differ between individuals, and defining which fraction of this variation can be attributed to the virus is important both clinically and epidemiologically. In this study, we show that the replication capacity of viruses isolated during acute infection predicts subsequent disease progression and drives CD4 decline independently of the viral load. This provides further support for the hypothesis that the replication capacity of the transmitted virus determines the initial damage to the immune system, setting the pace for later disease progression. However, we did not find evidence that the major structural gene gag drives this correlation, highlighting the importance of other genes in determining disease progression.

Project description:BackgroundThe efficacy of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is primarily ascribed as a source of neutralizing anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, the composition of other immune components in CCP and their potential roles remain largely unexplored. This study aimed to describe the composition and concentrations of plasma cytokines and chemokines in eligible CCP donors.MethodsA cross-sectional study was conducted among 20 prepandemic healthy blood donors without SARS-CoV-2 infection and 140 eligible CCP donors with confirmed SARS-CoV-2 infection. Electrochemiluminescence detection-based multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n = 35 analytes). A SARS-CoV-2 microneutralization assay was also performed. Differences in the percentage of detection and distribution of cytokine and chemokine concentrations were examined by categorical groups using Fisher's exact and Wilcoxon rank-sum tests, respectively.ResultsAmong CCP donors (n = 140), the median time since molecular diagnosis of SARS-CoV-2 was 44 days (interquartile range = 38-50) and 9% (n = 12) were hospitalized due to COVID-19. Compared with healthy blood donor controls, CCP donors had significantly higher plasma levels of interferon (IFN)-γ, interleukin (IL)-10, IL-15, IL-21, and macrophage-inflammatory protein-1, but lower levels of IL-1RA, IL-8, IL-16, and vascular endothelial growth factor-A (P < .0014). The distributions of plasma levels of IL-8, IL-15, and IFN-inducible protein-10 were significantly higher among CCP donors with high (≥160) versus low (<40) anti-SARS-CoV-2 neutralizing antibody titers (P < .0014). The median levels of IL-6 were significantly higher among CCP donors who were hospitalized versus nonhospitalized (P < .0014).ConclusionsHeterogeneity in cytokine and chemokine composition of CCP suggests there is a different inflammatory state among the CCP donors compared with SARS-CoV-2 naive, healthy blood donors.

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

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

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