Predictors of 007 triphosphate concentrations in dried blood spots in persons with hepatitis C and active drug or alcohol use.

BACKGROUND: Sofosbuvir is converted to its active form, 007 triphosphate (007-TP), within cells. To date, the association between treatment adherence and 007-TP in dried blood spots (DBS) and factors that influence this relationship remain unknown. OBJECTIVES: To examine relationships between adherence and 007-TP concentrations in DBS and identify factors that influence 007-TP in DBS. METHODS: Persons with HCV or HIV/HCV coinfection and self-reported drug and/or alcohol use were randomized to one of two technology-based approaches for monitoring 12 week adherence to once-daily ledipasvir/sofosbuvir. Convenience blood samples were collected every 2 weeks during treatment. 007-TP in DBS was quantified using LC/MS and analysed using mixed-effects models. RESULTS: A total of 337 observations were available from 58 participants (78% male; 21% black; 22% Hispanic/Latino; 26% cirrhotic; 78% HIV-coinfected). The mean half-life of 007-TP in DBS was 142 h (95% CI 127-156) and concentrations increased by 7.3% (95% CI 2.2-12.6) for every 10% increase in between-visit adherence. Geometric mean (95% CI) 007-TP concentrations in DBS were 301 (247-368), 544 (462-639) and 647 (571-723) fmol/punch by adherence categories of ≤50%, >50 to ≤80%, and >80%. Adherence, time on therapy, increasing age and decreased estimated glomerular filtration rate were associated with higher 007-TP, whereas increased time since last dose, male sex, black race and higher BMI were associated with lower 007-TP. CONCLUSIONS: 007-TP has an extended half-life in DBS and concentrations increased with adherence. Further research is needed to examine additional factors that affect 007-TP and the clinical utility of this measure.

Development and validation of an LC-MS/MS method to quantify the alcohol biomarker phosphatidylethanol 16:0/18:1 in dried blood spots for clinical research purposes.

Phosphatidylethanol (PEth) is a group of phospholipids detectable in red blood cells exclusively following ethanol consumption. The primary PEth analog, PEth 16:0/18:1, has an extended half-life in red cells, providing a long window of detection and tremendous potential for the quantification of cumulative alcohol consumption. We developed and validated an LC/MS-MS method to quantify PEth 16:0/18:1 in dried blood spots (DBS) for clinical research purposes. Method development and validation followed FDA guidance but expanded on prior published methods through the evaluation of additional DBS-specific factors such as sample hematocrit, punch location, and spot volume. This method was applied to the quantification of PEth in participant samples.

Adherence to Direct-Acting Antiviral Therapy in People Actively Using Drugs and Alcohol: The INCLUD Study.

BACKGROUND: Hepatitis C virus treatment in persons who use drugs (PWUD) is often withheld due to adherence and reinfection concerns. In this study, we report treatment outcomes, technology-based adherence data, and adherence predictors in PWUD and/or alcohol. METHODS: INCLUD was a prospective, open-label study of ledipasvir/sofosbuvir for 12 weeks in PWUD aged 18-70 years. Participants were randomized to wireless (wirelessly observed therapy) or video-based directly observed therapy (vDOT). Drug use was assessed every 2 weeks. Sustained virologic response (SVR) was examined by intention-to-treat and as-treated. Factors associated with missing ≥1 dose(s) between visits were examined using generalized linear models. RESULTS: Sixty participants received ≥1 ledipasvir/sofosbuvir dose (47 human immunodeficiency virus [HIV]/hepatitis C virus [HCV], 13 HCV only; 78% male; 22% black; 25% cirrhotic). Substance use occurred at 94% of person-visits: 60% marijuana, 56% alcohol, 37% methamphetamine, 22% opioids, 17% cocaine, and 20% injection drug use. The SVR by intention-to-treat was 86.7% (52 of 60) and as-treated was 94.5% (52 of 55). Confirmed failures included 1 relapse, 1 reinfection, and 1 unknown (suspected reinfection). Median total adherence was 96% (interquartile range [IQR], 85%-100%; range, 30%-101%), and between-visit adherence was 100% (IQR, 86%-100%; range, 0%-107%). The odds of missing ≥1 dose between visits increased with HIV coinfection (2.94; 95% confidence interval [CI], 1.37-6.32; P = .006), black race (4.09; 95% CI, 1.42-11.74; P = .009), methamphetamine use (2.51; 95% CI, 1.44-4.37; P = .0.001), and cocaine use (2.12; 95% CI, 1.08-4.18; P = .03) and decreased with marijuana use (0.34; 95% CI, 0.17-0.70; P = .003) and vDOT (0.43; 95% CI, 0.21-0.87; P = .02). CONCLUSIONS: Persons who use drugs achieved high SVR rates with high, but variable, ledipasvir/sofosbuvir adherence using technology-based methods. These findings support efforts to expand HCV treatment in PWUD.

Adiposity Indicators as Cardio-Metabolic Risk Predictors in Adults from Country with High Burden of Obesity.

BACKGROUND: In Qatar more than 70% 0f the adults are overweight and obese. Different adiposity assessment methods have been proposed to identify individuals at cardio-metabolic risk. PURPOSE: This study aimed to compare anthropometric indicators with Dual-energy X-ray absorptiometry (DXA) -derived adiposity indicators in predicting cardio-metabolic risk among Qatari adults. PATIENTS AND METHODS: A random sample of five hundred and fifty-eight (558) healthy Qatari adults (men and women) aged 20 to 50 years was obtained from Qatar Biobank survey data. Anthropometric data (weight, height, and waist circumference), the DXA-derived data, and cardio-metabolic (CM) risk parameters were analyzed. A Spearman partial correlation coefficient, Receiver Operating Characteristics (ROC) curve and an area under curve (AUC) were used to assess the predicting ability of adiposity indicators for CM risk factors. RESULTS: Adiposity indices (anthropometric and DXA) were significantly correlated with most of the CM indicators (r= -0.292 to 0.486, p< 0.001). The AUC of waist to height ratio (WHtR) was significantly higher than that of body mass index (BMI) and waist circumference (WC) in the prediction of low high density lipoprotein (HDL) (AUC=0.65, AUC=0.59; AUC=0.64), high low density lipoprotein (LDL) (AUC=0.67; AUC=0.62; AUC=0.66), high cholesterol (AUC=0.66; AUC=0.63; AUC=0.63), and high Homeostatic Model Assessment- (HOMA) (AUC= 0.81; AUC= 0.78; AUC=0.78). Among DXA- parameters, trunk fat had the highest AUCs for total cholesterol (AUC= 0.64, CI=0.56, 0.73), triglycerides and glucose index (TyG) (AUC=0.69, CI=0.64, 0.74), and HOMA (AUC=0.78, CI= 0.73, 0.84). CONCLUSION: Results of the present study show that adiposity indicators (WC and WHtR) are clinically valuable tools to identify individuals at risk of CVD compared to DXA-derived parameters, while DXA can provide more accurate estimates.