Association between bilirubin, atazanavir, and cardiovascular disease events among people living with HIV across the US.

Tue, 01 Jan 2019 00:00:00 GMT-06:00 - Crane, Heidi M; Nance, Robin M; Heckbert, Susan R; Ritchings, Corey; Rosenblatt, Lisa; Budoff, Matthew; Wood, Brian R.; Tirschwell, David L.; Kim, H Nina; Mathews, William C; Geng, Elvin; Moore, Richard D; Hunt, Peter W; Eron, Joseph J; Burkholder, Greer A; Drozd, Daniel R; Chow, Felicia C.; Becker, Kyra J.; Zunt, Joseph R.; Ho, Emily L.; Kalani, Rizwan; Huffer, Andrew; Whitney, Bridget M.; Saag, Michael S; Kitahata, Mari M; Delaney, Joseph AC
Θέμα: Bilirubin is an antioxidant that may suppress lipid oxidation. Elevated bilirubin is associated with decreased cardiovascular events in HIV-uninfected populations. We examined these associations in people living with HIV (PLWH).
Μέθοδοι: Potential myocardial infarctions (MI) and strokes were centrally adjudicated. We examined MI types: Type 1 MI (T1MI) from atherosclerotic plaque instability and Type 2 MI (T2MI) in the setting of oxygen demand/supply mismatch such as sepsis. We used multivariable Cox regression analyses to determine associations between total bilirubin levels and outcomes adjusting for traditional and HIV-specific risk factors. To minimize confounding by hepatobiliary disease we conducted analyses limited to bilirubin values<2.1 mg/dl; among those with Fibrosis-4 values<3.25; and among everyone. We repeated analyses stratified by hepatitis C status and time-updated atazanavir use.
Αποτελέσματα: Among 25,816 PLWH, there were 392 T1MI and 356 T2MI during follow-up. Adjusted hazard ratios (HR) for the association of higher bilirubin levels with T1MI were not significant. Higher bilirubin levels were associated with T2MI. In contrast, among PLWH on atazanavir, higher bilirubin levels were associated with fewer T2MI (HR 0.56:0.33-1.00). Higher bilirubin levels among those on atazanavir were associated with fewer T1MI combined with ischemic stroke. Limitations: Analyses were conducted with total rather than unconjugated bilirubin.
Συμπέρασμα: Among PLWH, higher bilirubin levels were associated with T2MI among some subgroups. However, among those on atazanavir, there was a protective association between bilirubin and T2MI. These findings demonstrate different associations between outcomes and elevated bilirubin due to diverse causes and the importance of distinguishing MI types. Conflicts of Interest and Source of Funding: This work was supported by Brystol-Myers Squibb. Additional support came from the National Institute of Allergy and Infectious Diseases (CNICS R24 AI067039, UW CFAR NIAID Grant P30 AI027757; UNC CFAR grant P30 AI50410, JHU CFAR grant P30 AI094189, and UAB CFAR grant P30 AI027767), the National Institute of Drug Abuse (U01DA036935) and the National Heart, Lung, and Blood Institute [R01HL126538] at the National Institutes of Health and from the American Heart Association (13GRNT14560022). The following have received grant support or served as consultants or advisors: Dr. Hunt with Merck and Gilead, Dr. Burkholder with DefiniCare, Dr. Saag with BMS, Gilead, Merck, and ViiV, Dr. Moore with Medscape, Dr. Eron with Merck, ViiV, BMS, Abbvie, Gilead, Tibotec/Janssen, Dr. Drozd with Gilead, Dr. Crane with ViiV, and Dr. Budoff has consulted for General Electric. The following are affiliated with BMS: C Ritchings, L Rosenblatt. - Β© 2019

Field suitability and diagnostic accuracy of the BiocentricΒ® open real-time PCR platform for dried blood spot (DBS)-based HIV viral load quantification in Eswatini

Tue, 01 Jan 2019 00:00:00 GMT-06:00 - Kerschberger, Bernhard; Ntshalintshali, Nombuso; Mpala, Qhubekani; DΓ­az Uribe, Paola Andrea; Maphalala, Gugu; Kalombola, Sydney; Bekele, Addis; Chawinga, Tiwonge; Maphalala, Mukelo; Jani, Aditi; Phugwayo, Nomcebo; Tour, Roberto de la; Nyoni, Nomxolise; Goiri, Javier; Dlamini, Sindisiwe; Ciglenecki, Iza; Fajardo, Emmanuel
Εισαγωγή: To assess the performance and suitability of dried blood spot (DBS) sampling using filter paper to collect blood for viral load (VL) quantification under routine conditions.
Μέθοδοι: We compared performance of DBS VL quantification using the Biocentric method with plasma VL quantification using Roche and Biocentric as reference methods. Adults (≥18 years) were enrolled at two health facilities in Eswatini from 12 October 2016 to 1 March 2017. DBS samples were prepared through finger-prick by a phlebotomist (DBS-1), and through pipetting of whole venous blood by a phlebotomist (DBS-2) and by a laboratory technologist (DBS-3). We calculated the VL testing completion rate, correlation, and agreement, as well as diagnostic accuracy estimates at the clinical threshold of 1000 copies/mL.
Αποτελέσματα: Of 362 patients enrolled, 1066 DBS cards (DBS-1: 347; DBS-2: 359; DBS-3: 360) were tested. Overall, test characteristics were comparable between DBS sampling methods and irrespective of reference method. The Pearson’s correlation coefficients ranged from 0.67 to 0.82 (p<0.001) for different types of DBS sampling on both reference methods, and the Bland–Altman difference ranged from 0.15 to 0.30 log10 copies/mL. Sensitivity estimates were from 85.3% to 89.2% and specificity estimates were from 94.5 to 98.6%. The positive predictive values were between 87.0% and 96.5% at a prevalence of 30% VL elevations, and negative predictive values were between 93.7% and 95.4%.
Συμπεράσματα: DBS VL quantification using the newly-configured Biocentric method can be part of contextualized VL testing strategies, particularly for remote settings and populations with higher viral failure rates. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Corresponding author: Bernhard Kerschberger; P.O. Box 18, Eveni, Lot No. 331, Sheffield Road, Industrial Area, Mbabane, Eswatini Email:; Cell: 00268-78151718 Conflicts of Interest and Source of Funding: The authors have no personal funding or conflicts of interest to disclose. Most of the study was funded by Unitaid, and Biocentric donated some viral load testing consumables and devices. The funding sources (Unitaid, Biocentric) did not play any role in the design of the study, data collection, analyses, and interpretation of data or in the writing of the manuscript or the decision to publish the findings. - Β© 2019

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