Serial limiting dilution (SLD) assays are used in many areas of infectious disease related research. This paper presents SLDAssay, a free and publicly available R software package and web tool for analyzing data from SLD assays. SLDAssay computes the maximum likelihood estimate (MLE) for the concentration of target cells, with corresponding exact and asymptotic confidence intervals. Exact and asymptotic goodness of fit p-values, and a bias-corrected (BC) MLE are also provided. No other publicly available software currently implements the BC MLE or the exact methods. For validation of SLDAssay, results from Myers et al. (1994) are replicated. Simulations demonstrate the BC MLE is less biased than the MLE. Additionally, simulations demonstrate that exact methods tend to give better confidence interval coverage and goodness-of-fit tests with lower type I error than the asymptotic methods. Additional advantages of using exact methods are also discussed.
Background Quantifying tissue drug concentrations can yield important information during drug development, but complicates pharmacokinetic study design. Mucosal fluids collected by direct aspiration(cervicovaginal fluid; CVF) or swab(rectal fluid; RF) might be used as tissue concentration surrogates, but these relationships are not well characterized. Methods Forty-nine healthy women, given a single oral dose of tenofovir, maraviroc, emtricitabine, or raltegravir at 50% to 200% of the treatment dose, provided 13 plasma, 12 CVF, 12 RF and one cervical, vaginal and rectal tissue biopsy over 48hrs. Relationships between these paired samples were characterized by linear and multiple linear regression. Adjusted r2 values were used to select the final predictive models. Results CVF exposure increased linearly with dose for all antiretrovirals (r2≥0.23, p≤0.02) except raltegravir (r2=0.08, p=0.19). In RF, only emtricitabine increased linearly with dose (r2=0.27, p=0.01). For all antiretrovirals, CVF and RF concentrations significantly correlated with mucosal tissue concentrations (female genital tract r2≥0.37, rectal tissue r2≥0.50; p≤0.001). In the final multivariate models, plasma and fluid concentrations were both associated with FGT concentrations for all antiretrovirals (r2≥0.81; p<0.001). The same was noted for rectal tissue (r2≥0.58; p<0.001) except for tenofovir, for which RF alone was predictive of tissue concentration (r2=0.91; p<0.001). Conclusions Mucosal fluids were positively correlated with tissue concentrations, and including plasma concentrations improved the regression models in most cases. Dose linearity in CVF, but not RF, suggests a saturation process in lower gastrointestinal tract tissue. These findings suggest that mucosal fluid and plasma concentrations may be used for qualitative inference of tissue concentrations for these antiretrovirals.
Background.Although rates of sustained virologic response (SVR) after hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) surpass 90% in trials and some more “real world” settings, some patients, such as those with substance use disorders, will be challenged to adhere to HCV care.Methods.To assess the feasibility of 2 strategies for financially incentivizing adherence to HCV care, patients with a substance use history prescribed 12 weeks of a sofosbuvir-containing regimen were randomized to either fixed or lottery-based monetary incentives for attending clinic appointments, pill count adherence >90%, and SVR achievement. Electronic medication monitoring provided an objective measure of DAA adherence.Results.Fifty-nine participants were randomized to the lottery (n = 31) or fixed-incentive (n = 28) arms. All 31 (100%) in the lottery arm and 24 of 28 (86%) in the fixed arm completed 12 weeks of therapy. By intent-to-treat, 93% in the lottery arm and 92% in the fixed arm achieved SVR (estimated difference: 0.5%; 95% confidence interval, −17.5 to 18.8). Overall, 92% of scheduled visits were attended without significant differences between arms. The mean adherence ratio (days with ≥1 bottle opening:monitored days) was 0.91 for lottery and 0.92 for fixed arms.Conclusions.In this pilot, fixed- and lottery-based financial incentives were successfully implemented and accepted by patients with a substance use history. High levels of HCV therapy and care adherence, as well as rates of SVR, were observed. Financial incentives may be useful to support treatment adherence in patients with substance use disorders and should be tested in a larger, randomized, controlled trial.
Antiretroviral therapy (ART) requires lifelong daily oral therapy. While patient characteristics associated with suboptimal ART adherence and persistence have been described in cohorts of HIV-infected persons, these factors are poor predictors of individual medication taking behaviors. We aimed to create and test instruments for the estimation of future ART adherence and persistence for clinical and research applications. Following formative work, a battery of 148 items broadly related to HIV infection and treatment was developed and administered to 181 HIV-infected patients. ART adherence and persistence were assessed using electronic monitoring for 3 months. Perceived confidence in medication taking and self-reported barriers to adherence were strongest in predicting non-adherence over time. Barriers to adherence (e.g., affordability, scheduling) were the strongest predictors of non-adherence, as well as 3- and 7-day non-persistence. A ten-item battery for prediction of these outcomes ( www.med.unc.edu/ncaidstraining/adherence/for-providers ) and a 30-item battery reflective of underlying psychological constructs can help identify and study individuals at risk for suboptimal ART adherence and persistence.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.