Soluble biomarkers of immune activation and inflammation in <scp>HIV</scp> infection: impact of 2 years of effective first‐line combination antiretroviral therapy

Hattab, Suhaib; Guiguet, Marguerite; Carcelain, Guislaine; Fourati, Slim; Guihot, Amélie; Autran, Brigitte; Caby, Fabienne; Marcelin, Anne–Geneviève; Costagliola, Dominique; Katlama, Christine

doi:10.1111/hiv.12257

Cited by 53 publications

(50 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…High plasma IP-10, IL-6 and sCD14 all consistently predict increased subsequent morbidity and mortality during ART [42, 43, 60], and high sCD163 levels have been associated with surrogate markers of neurologic and cardiovascular disease (though perhaps not cardiovascular events [61]), as well as all-cause mortality in a recent report [26, 57–59, 62, 63]. As many of these biomarkers of monocyte activation may be increased by smoking and/or alcohol use, many of these associations with morbidity and mortality may be at least in part driven by behavioral risk factors and not HIV itself, though a recent report suggests that these associations persist despite adjustment for behavioral risk factors [64].…”

Section: Specific Immunologic Pathways That Predict Disease In Hiv Inmentioning

confidence: 99%

Role of immune activation in progression to AIDS

Utay

Hunt

2016

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

Purpose of the review To review recent insights into the impact of HIV-associated immune activation on AIDS and non-AIDS morbidity and mortality. Recent findings Immune activation has long been recognized as an important consequence of untreated HIV infection and predictor of AIDS progression, which declines but fails to normalize during suppressive antiretroviral therapy (ART), and continues to predict disease in this setting. Thus, a major research agenda is to develop novel therapies to reduce persistent immune activation in treated HIV infection. Yet, the optimal targets for interventions remain unclear. Both the specific root causes of immune activation and the many interconnected pathways of immune activation that are most likely to drive disease risk in HIV-infected individuals remain incompletely characterized, but recent studies have shed new light on these topics. Summary In the context of this review, we will summarize recent evidence helping to elucidate the immunologic pathways that appear most strongly predictive of infectious and non-infectious morbidity. We will also highlight the likelihood that not all root drivers of immune activation - and the discrete immunologic pathways to which they give rise - are likely to produce the same disease manifestations and/or be equally attenuated by early ART initiation.

show abstract

Section: Specific Immunologic Pathways That Predict Disease In Hiv Inmentioning

confidence: 99%

Role of immune activation in progression to AIDS

Utay

Hunt

2016

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

show abstract

“…Epidemiological studies demonstrated that while endothelial dysfunction is reduced following HAART initiation, long term exposure to ARVd leads to the development of vasculopathy, especially with the usage of certain protease inhibitors3435. These conditions could arise from chronic induction of ER stress3637, an increase in local inflammation38, or apoptosis activation39.…”

mentioning

confidence: 99%

Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity

Bertrand

Dygert

Toborek

2016

Sci Rep

View full text Add to dashboard Cite

The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke. Among studied drugs, Efavirenz, but not other NNRTIs, altered claudin-5 expression, increased endothelial permeability, and disrupted the blood-brain barrier integrity. Importantly, Efavirenz exposure increased the severity of stroke in a model of middle cerebral artery occlusion in mice. Taken together, these results indicate that selected ARVd can exacerbate HIV-associated cerebrovascular pathology. Therefore, careful consideration should be taken when choosing an anti-retroviral therapy regimen.

show abstract

“…Upon ART initiation, immune activation is only partially attenuated, and not equally among all people [9–12]. We hypothesized that a subset of immune activation biomarkers measurable in ART initiators would not be suppressed by ART and might predict clinical failure.…”

mentioning

confidence: 99%

Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort

Balagopal

Gupte

Shivakoti

et al. 2016

Open Forum Infectious Diseases

View full text Add to dashboard Cite

Background. We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings.Methods. We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incident World Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (>Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis.Results. Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/µL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27–7.20), sCD14 (IRR, 2.17; 95% CI, 1.02–4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01–0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated.Conclusions. Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function.

show abstract

Soluble biomarkers of immune activation and inflammation in HIV infection: impact of 2 years of effective first‐line combination antiretroviral therapy

Abstract: The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.

Cited by 53 publications

References 40 publications

Role of immune activation in progression to AIDS

Role of immune activation in progression to AIDS

Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity

Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort

Contact Info

Product

Resources

About