Computerized Adjudication of Coronary Heart Disease Events Using the Electronic Medical Record in HIV Clinical Research: Possibilities and Challenges Ahead

This pilot study assessed feasibility of computer-assisted electronic medical record (EMR) abstraction to ascertain coronary heart disease (CHD) event hospitalizations. We included a sample of 87 hospitalization records from participants the University of North Carolina (UNC) site of the Women's Interagency HIV Study (WIHS) and UNC Center for AIDS Research (CFAR) HIV Clinical Cohort who were hospitalized within UNC Healthcare System from July 2004 to July 2015. We compared a computer algorithm utilizing diagnosis/procedure codes, medications, and cardiac enzyme levels to adjudicate CHD events [myocardial infarction (MI)/coronary revascularization] from the EMR to standardized manual chart adjudication. Of 87 hospitalizations, 42 were classified as definite, 25 probable, and 20 non-CHD events by manual chart adjudication. A computer algorithm requiring presence of ≥1 CHD-related International Classification of Diseases, 9th Revision (ICD-9)/Current Procedural Terminology (CPT) code correctly identified 24 of 42 definite (57%), 29 of 67 probable/definite CHD (43%), and 95% of non-CHD events; additionally requiring clinically defined cardiac enzyme levels or administration of MI-related medications correctly identified 55%, 42%, and 95% of such events, respectively. Requiring any one of the ICD-9/CPT or cardiac enzyme criteria correctly identified 98% of definite, 97% of probable/definite CHD, and 85% of non-CHD events. Challenges included difficulty matching hospitalization dates, incomplete diagnosis code data, and multiple field names/locations of laboratory/medication data. Computer algorithms comprising only ICD-9/CPT codes failed to identify a sizable proportion of CHD events. Using a less restrictive algorithm yielded fewer missed events but increased the false-positive rate. Despite potential benefits of EMR-based research, there remain several challenges to fully computerized adjudication of CHD events

Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results

Etravirine (ETR), an NNRTI approved for 200 mg BID dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing

Raltegravir Pharmacokinetics in Treatment-Naive Patients Is Not Influenced by Race: Results from the Raltegravir Early Therapy in African-Americans Living with HIV (REAL) Study

Racial differences in antiretroviral treatment responses remain incompletely explained and may be a consequence of differential pharmacokinetics (PK) associated with race. Raltegravir, an inhibitor of HIV-1 integrase, is commonly used in the treatment of HIV-infected patients, many of whom are African-American. However, there are few data regarding the PK of raltegravir in African-Americans. HIV-infected men and women, self-described as African-American and naive to antiretroviral therapy were treated with raltegravir (RAL) at 400 mg twice a day, plus a fixed dose of tenofovir-emtricitabine (TDF/FTC) at 300 mg/200 mg once daily. Intensive PK sampling was conducted over 24 h at week 4. Drug concentrations at two trough values of 12 and 24 h after dosing (C12 and C24), area under the concentration-curve values (AUC), maximum drug concentration (Cmax), and the time at which this concentration occurred (Tmax) in plasma were estimated with noncompartmental pharmacokinetic methods and compared to data from a subset of white subjects randomized to the RAL twice a day (plus TDF/FTC) arm of the QDMRK study, a phase III study of the safety and efficacy of once daily versus twice daily RAL in treatment naive patients. A total of 38 African-American participants were enrolled (90% male) into the REAL cohort with the following median baseline characteristics: age of 36 years, body mass index (BMI) of 23 kg/m2, and a CD4 cell count of 339/ml. Plasma HIV RNA levels were below 200 copies/ml in 95% of participants at week 4. The characteristics of the 16 white QDMRK study participants were similar, although fewer (69%) were male, the median age was higher (45 years), and BMI was lower (19 kg/m2). There was considerable interindividual variability in RAL concentrations in both cohorts. Median C12 in REAL was 91 ng/ml (range, 10 to 1,386) and in QDMRK participants was 128 ng/ml (range, 15 to 1,074). The Cmax median concentration was 1,042 ng/ml (range, 196 to 10,092) for REAL and 1,360 ng/ml (range, 218 to 9,701) for QDMRK. There were no significant differences in any RAL PK parameter between these cohorts of African-American and white individuals. Based on plasma PK, and with similar adherence rates, the performance of RAL among HIV-infected African-Americans should be no different than that of infected patients who are white

Evaluation of endothelial function and subclinical atherosclerosis in association with hepatitis C virus in HIV-infected patients: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Relationship of hepatitis C virus (HCV) infection with an increased risk of cardiovascular disease (CVD) in HIV-infected patients remains controversial. We evaluated endothelial function and subclinical atherosclerosis in HIV-infected patients with and without HCV.</p> <p>Methods</p> <p>Flow-mediated dilatation (FMD) of the brachial artery and circulating levels of cell adhesion molecules (CAM) were measured in HCV/HIV-coinfected and HIV-monoinfected patients. Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT).</p> <p>Results</p> <p>63 (31%) HCV/HIV-coinfected and 138 (69%) HIV-monoinfected patients were included. Median soluble vascular CAM-1 (sVCAM-1) and intercellular CAM-1 (sICAM-1) levels were significantly higher in HIV/HCV-coinfected patients (P < 0.001 for both cases). Median (interquartile range) FMD was 6.21% (2.86-9.62) in HCV/HIV-coinfected and 5.54% (2.13-9.13) in HIV-monoinfected patients (P = 0.37). Adjustment for variables associated with HCV and FMD disclosed similar results. FMD correlated inversely with cIMT and age. Carotid IMT did not differ between HCV/HIV-coinfected and HIV-monoinfected patients in unadjusted (0.61 [0.55-0.65] mm vs 0.60 [0.53-0.72] mm; P = 0.39) or adjusted analyses.</p> <p>Conclusion</p> <p>HCV infection was associated with higher levels of sICAM-1 and sVCAM-1, but no evidence of increased subclinical atherosclerosis was found when endothelial function was evaluated through FMD, or when assessing the cIMT.</p

Do interventions to improve adherence to antiretroviral therapy recognise diversity? A systematic review

People living with HIV (PLWH) are often culturally and linguistically diverse populations; these differences are associated with differing barriers to antiretroviral therapy (ART) adherence. Cultural competence measures the extent to which trial design recognises this diversity. This systematic review aimed to determine whether adherence trial participants represent the diversity of PLWH. Randomised Controlled Trials in Organisation for Economic Co-operation and Development countries to improve ART adherence were eligible. We searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. For all included trials, we searched for their development, testing and evaluation studies. We compared trial participant characteristics with nationally reported PLWH data. We appraised trial cultural competence against ten criteria; scoring each criterion as 0, 1 or 2 indicating cultural blindness, pre-competence or competence respectively. For 80 included trials, a further 13 studies presenting development/testing/evaluation data for the included trials were identified. Only one of the 80 included studies reported trial participants representative of the country's population of PLWH. The median (IQ) cultural competence score was 2.5 (1.0, 4.0) out of 20. HIV adherence trial participants are not reflective of the population with HIV, which may be due to limited adoption of culturally competent research methods

Increased glucose transporter-1 expression on intermediate monocytes from HIV-infected women with subclinical cardiovascular disease

People living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes up-regulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition