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.