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

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

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

Comparison of postoperative intraocular pressure in patients with Densiron-68 vs conventional silicone oil: a case-control study

A solution of perfluorohexyloctane and silicone oil with a specific gravity of 1.06 g/cm(3) (Densiron-68) has similar properties as conventional silicone oil ( SO) in terms of the shape of the bubble and its ability to act as an internal tamponade agent. We conducted a case-control study to compare the postoperative intraocular pressure (IOP) in patients treated with Densiron-68 with those treated with SO. Methods Seventy-one eyes of 71 patients and 57 eyes of 57 patients who had received Densiron-68 and SO, respectively, were included in our study. Both groups were found to have matched for their preoperative comorbidities ( diabetes, glaucoma, phakic status, and refractive errors). IOP at first day, between seventh and fourteenth day, and at 4 week postoperatively was recorded. Results The mean IOP was higher in patients treated with Densiron-68 at day 1 and between seventh and fourteenth day postoperatively (P = 0.05 and 0.01, respectively). By the 4th week, the IOP difference between the two groups was insignificant (P = 0.17). The difference in the two groups could still be clinically significant and the raised IOP in Densiron-68 group was more difficult to treat in some cases. On day 1, nine eyes (12.7%) in the Densiron-68 group and two eyes (3.5%) in the SO group had IOP greater than 30 mmHg. At 4 weeks, IOP of more than 30 mmHg was seen in nine eyes ( 12.7%) in the Densiron-68-treated group and in one eye (1.8%) in the SO group. Conclusion The use of Densiron-68 was associated with a higher IOP in the early postoperative period when compared with SO

Comparison of postoperative intraocular pressure in patients with Densiron-68 vs conventional silicone oil: a case–control study

A solution of perfluorohexyloctane and silicone oil with a specific gravity of 1.06 g/cm3 (Densiron-68) has similar properties as conventional silicone oil (SO) in terms of the shape of the bubble and its ability to act as an internal tamponade agent. We conducted a case-control study to compare the postoperative intraocular pressure (IOP) in patients treated with Densiron-68 with those treated with SO. Methods: Seventy-one eyes of 71 patients and 57 eyes of 57 patients who had received Densiron-68 and SO, respectively, were included in our study. Both groups were found to have matched for their preoperative comorbidities (diabetes, glaucoma, phakic status, and refractive errors). IOP at first day, between seventh and fourteenth day, and at 4 week postoperatively was recorded. Results: The mean IOP was higher in patients treated with Densiron-68 at day 1 and between seventh and fourteenth day postoperatively (P=0.05 and 0.01, respectively). By the 4th week, the IOP difference between the two groups was insignificant (P=0.17). The difference in the two groups could still be clinically significant and the raised IOP in Densiron-68 group was more difficult to treat in some cases.On day 1, nine eyes (12.7%) in the Densiron-68 group and two eyes (3.5%) in the SO group had IOP greater than 30 mmHg. At 4 weeks, IOP of more than 30 mmHg was seen in nine eyes (12.7%) in the Densiron-68-treated group and in one eye (1.8%) in the SO group. Conclusion: The use of Densiron-68 was associated with a higher IOP in the early postoperative period when compared with SO. © 2009 Macmillan Publishers Limited All rights reserved.link_to_subscribed_fulltex