Higher Levels of CRP, D-dimer, IL-6, and Hyaluronic Acid Before Initiation of Antiretroviral Therapy (ART) Are Associated With Increased Risk of AIDS or Death

Boulware, David R.; Hullsiek, Katherine Huppler; Puronen, Camille E.; Rupert, Adam; Baker, Jason V.; French, Martyn A.; Bohjanen, Paul R.; Novak, Richard M.; Neaton, James D.; Sereti, Irini

doi:10.1093/infdis/jir134

Cited by 280 publications

(288 citation statements)

References 36 publications

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“…Moreover, high level of CRP was a risk factor of IRIS. 15 These results were inconsistent with our findings. Therefore, if increased levels of CRP, ESR and LDH are found in HIV/TB co-infected patients, some features including the duration of HAART treatment, clinical symptoms, CD4 + cell counts and HIV RNA loads should be considered along with the infection to comprehensively evaluate the possibility of developing IRIS and to help make the most appropriate early treatment strategy.…”

Section: Discussioncontrasting

confidence: 95%

Analysis of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in HIV/TB Co-infected Patients During HAART

Zhou¹,

Wang²,

Li³

et al. 2014

Infection International

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Objectives To investigate the clinical features of tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (TB-IRIS) in patients co-infected with HIV/TB or latent infection during highly active antiretroviral therapy (HAART). Methods HIV-infected patients treated in the Third People’s Hospital of Shenzhen, China between March 2012 and March 2013 were recruited, and divided into 3 groups: 1) HIV/TB co-infection group (n = 50), 2) HIV/ MTB latent infection group (n = 50), and 3) HIV infection group (n = 50), with 12-month follow-up. Patients in the HIV/TB co-infection group were treated with HAART 2 weeks after TB therapy. Patients were assessed at different time-points. Results The incidence and mortality rates of TB-IRIS were 40% and 10% in the HIV/TB co-infected patients, and 2% (and no mortality) in the HIV/MTB group. The HIV infected group did not display TB-IRIS or death. About 95% HIV/TB co-infected patients were 20-39 years old when TB-IRIS occurred, and 65% of the patients developed TB-IRIS 2 weeks after HAART. For the co-infection group, those with TB-IRIS (20/20, 100%) had fever, with a significantly higher incidence than those who did not develop TB-IRIS (6.7%, 2/30, P < 0.05). The patients with TB-IRIS in co-infection group displayed markedly higher clinical biochemical markers, acute phase reactants, increased CD4+ cell counts, and 2 log10-decreases of HIV RNA loads, compared with the patients not presenting with TB-IRIS (P < 0.05). Conclusion HIV/TB co-infected patients presented with a high-risk of developing TB-IRIS during HAART treatment. Early diagnosis and treatment could decrease mortality rates in TB-IRIS.

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Section: Discussioncontrasting

confidence: 95%

Analysis of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in HIV/TB Co-infected Patients During HAART

Zhou¹,

Wang²,

Li³

et al. 2014

Infection International

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“…3,4 Meanwhile, three types of arguments have emerged to support even earlier initiation of ART. First, there is increasing documentation of inflammation in people with uncontrolled viral replication and of non-acquired immunodeficiency syndrome (AIDS)-defining noninfectious diseases as causes of death in HIV-infected persons 5,6 (with AIDS-defining diseases identified as diseases included in the Centers for Disease Control and Prevention case definition of AIDS 7 ). Second, among patients living with HIV in lower-resource countries, the rates of tuberculosis and bacterial diseases are high.…”

mentioning

confidence: 99%

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

2015

N Engl J Med

1,020

447

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BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

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“…The higher secretion of IL-6, which is considered an activator of the acute phase responses [27] and also a marker of critical illness during influenza infection [28,5], may also explain the more severe clinical outcomes reported in HIV-negative patients, supporting the hypothesis that clinical complications following influenza infection may result from an inflammatory burst. It was shown that higher levels of IL-6 in pre-HAART HIV patients correlate with higher morbidity and mortality rates [29]. These data suggest that IL-6 can effectively be considered as a valuable marker of severe infection.…”

Section: Discussionmentioning

confidence: 92%

Immune response to influenza A(H1N1)v in HIV-infected patients

Sansonetti

Sali

Fabbiani

et al. 2014

J Infect Dev Ctries

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Introduction: HIV infection is considered a risk factor for severe outcomes of influenza A(H1N1)v infection. However, data on immune response against influenza A(H1N1)v virus in HIV-infected patients are lacking. Methodology: Data from seven HIV-positive and 14 HIV-negative patients infected with A(H1N1)v and from 23 HIV-positive and six HIV-negative asymptomatic controls were analyzed to evaluate the clinical picture, A(H1N1)v viral shedding, and the immune response against the virus. Results: Patients displayed mainly upper respiratory tract diseases (57.1%), while pneumonia was diagnosed only in HIV-negative patients (23.8% of subjects, of which 4.8% required intensive care unit admission). At day seven, 29% of HIV-infected patients were still positive for A(H1N1)v by RT-PCR on nasopharyngeal swabs. Interestingly, a persistence of CXCL10 secretion at high level and lower IL-6 levels was observed in HIV-positive subjects. The geometric mean haemagglutination inhibition titer (HI-GMT) and anti-influenza IgM levels were lower in HIV-positive individuals while anti-influenza IgG levels remained similar in the two groups. Conclusions: The immune impairment due to HIV infection could affect A(H1N1)v clearance and could lead to a lower antibody response and a persistent secretion of CXCL10 at high levels. However, the lower IL-6 secretion and treatment with highly active antiretroviral therapy (HAART) could result in a milder clinical picture.

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Higher Levels of CRP, D-dimer, IL-6, and Hyaluronic Acid Before Initiation of Antiretroviral Therapy (ART) Are Associated With Increased Risk of AIDS or Death

Abstract: Biomarkers of Inflammation (CRP, IL-6), coagulation (D-dimer), and tissue fibrosis (HA) measured pre-ART and at 1 month are associated with higher risk of AIDS events, IRIS, or death, warranting additional study as risk stratification strategies.

Cited by 280 publications

References 36 publications

Analysis of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in HIV/TB Co-infected Patients During HAART

Analysis of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in HIV/TB Co-infected Patients During HAART

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

Immune response to influenza A(H1N1)v in HIV-infected patients

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