11 research outputs found

    Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

    Get PDF
    Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

    Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

    Get PDF
    Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

    Supplementary Data for the Paper: Description of comprehensive dental services supported by the Medicare Chronic Disease Dental Scheme In the first twenty three months of operation, In Press: The ANZ Journal of Public Health

    No full text
    The two tables provided show details at the state and territory level, of information presented only at the National level in Tables 1 and 2 of the paper entitled: Description of comprehensive dental services supported by the Medicare Chronic Disease Dental Scheme In the first twenty three months of operation, which is published by the Australian and New Zealand Journal of Public Health (2011, In Press). Tables show: The number of Medicare Chronic Disease Dental Scheme supported patients and services according to treatment type (Table 2); and The average number of Medicare Chronic Disease Dental Scheme services per patient according to type of service delivered, expressed as both services per patient and the relative percentage of services per patient (Table 3). Details on how this data was collected, as well as how it was interpreted and other relevant information are available in the complete manuscript published by the ANZJPH, 2011 (In Press)

    Description of comprehensive dental services supported by the Medicare Chronic Disease Dental Scheme in the first 23 months of operation

    No full text
    Abstract Objective: Australia's Medicare universal insurance system has supported comprehensive dental service through the Chronic Disease Dental Scheme (CDDS) since November 2007. Public debate opposing CDDS includes claims of over‐servicing, calls for expansion to universal eligibility, and government threat of closure. Here we examine CDDS services over the first 23 months of operation. Methods: CDDS statistics on patient age, gender and item numbers claimed from November 2007 to December 2009 from Medicare were subjected to analysis. Results: The distribution of 404,768 total CDDS patients varied across Australia from 3.6% of the population in NSW to 0.07% in NT, while uptake increased over time. The average patient had 7.58 dental treatments, and the most common were: direct restorations (2.27), preventive and periodontal services (1.46), diagnostic services (1.43), extractions (0.77), and new dentures (0.53). Crown and bridgework appeared over‐represented (0.48). Conclusion: Although data do suggest over‐servicing in crown and bridgework, there also appears to be significant community need for the CDDS. Implication: Clear guidelines for dental clinical diagnosis and treatment planning, as well as a pre‐approval process for crown and bridgework is suggested to improve the CDDS, and this could form the basis for expansion to universal eligibility for dental Medicare

    Interruption of antiretroviral therapy is associated with increased plasma cystatin C.

    No full text
    Collaboratore della suddetta ricerca in quanto membro del INSIGHT SMART Study Grou

    Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up.

    No full text
    Collaboratore per la suddetta ricerca in quanto membro di SMART Study Grou

    Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial.

    No full text
    Collaboratore per la suddetta ricerca multicentrica in quanto membro di SMART Study Grou

    Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen.

    No full text
    Collaboratore per la suddetta ricerca multicentrica in quanto membro di SMART Study Group

    Interleukin-2 therapy in patients with HIV infection

    No full text
    Collaboratore per la suddetta ricerca multicentrica in quanto membro del INSIGHT-ESPRIT Study Grou

    Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

    No full text
    10.1371/journal.pone.0139981PLoS ONE1010e013998
    corecore