scholarly journals A Bayesian natural cubic B-spline varying coefficient method for non-ignorable dropout

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Camille M. Moore ◽  
Samantha MaWhinney ◽  
Nichole E. Carlson ◽  
Sarah Kreidler
Keyword(s):  
Clinical Trials ◽  
Viral Load ◽  
Drug Use ◽  
Cohort Studies ◽  
Cell Count ◽  
Parametric Model ◽  
Parametric Models ◽  
Viral Load Suppression ◽  
The Impact ◽  
Over Time

Abstract Background Dropout is a common problem in longitudinal clinical trials and cohort studies, and is of particular concern when dropout occurs for reasons that may be related to the outcome of interest. This paper reviews common parametric models to account for dropout and introduces a Bayesian semi-parametric varying coefficient model for exponential family longitudinal data with non-ignorable dropout. Methods To demonstrate these methods, we present results from a simulation study and estimate the impact of drug use on longitudinal CD4 + T cell count and viral load suppression in the Women’s Interagency HIV Study. Sensitivity analyses are performed to consider the impact of model assumptions on inference. We compare results between our semi-parametric method and parametric models to account for dropout, including the conditional linear model and a parametric frailty model. We also compare results to analyses that fail to account for dropout. Results In simulation studies, we show that semi-parametric methods reduce bias and mean squared error when parametric model assumptions are violated. In analyses of the Women’s Interagency HIV Study data, we find important differences in estimates of changes in CD4 + T cell count over time in untreated subjects that report drug use between different models used to account for dropout. We find steeper declines over time using our semi-parametric model, which makes fewer assumptions, compared to parametric models. Failing to account for dropout or to meet parametric assumptions of models to account for dropout could lead to underestimation of the impact of hard drug use on CD4 + cell count decline in untreated subjects. In analyses of subjects that initiated highly active anti-retroviral treatment, we find that the estimated probability of viral load suppression is lower in models that account for dropout. Conclusions Non-ignorable dropout is an important consideration when analyzing data from longitudinal clinical trials and cohort studies. While methods that account for non-ignorable dropout must make some unavoidable assumptions that cannot be verified from the observed data, many methods make additional parametric assumptions. If these assumptions are not met, inferences can be biased, making more flexible methods with minimal assumptions important.

scholarly journals STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lorena Leticia Peixoto de Lima ◽  
Allysson Quintino Tenório de Oliveira ◽  
Tuane Carolina Ferreira Moura ◽  
Ednelza da Silva Graça Amoras ◽  
Sandra Souza Lima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Α Level ◽  
The Impact ◽  
Hiv 1

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

Failure to achieve a CD4+ cell count response on combination antiretroviral therapy despite consistent viral load suppression

AIDS ◽  
2014 ◽  
Vol 28 (6) ◽  
pp. 919-924 ◽  
Author(s):  
Jemma L. O’Connor ◽  
Colette J. Smith ◽  
Fiona C. Lampe ◽  
Teresa Hill ◽  
Mark Gompels ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Combination Antiretroviral Therapy ◽  
Viral Load Suppression ◽  
Cd4 Cell Count ◽  
Count Response ◽  
Cd4 Cell

scholarly journals Model Averaging with AIC Weights for Hypothesis Testing of Hormesis at Low Doses

Dose-Response ◽  
2017 ◽  
Vol 15 (2) ◽  
pp. 155932581771531
Author(s):  
Steven B. Kim ◽  
Nathan Sanders
Keyword(s):  
Hypothesis Testing ◽  
Dose Response ◽  
Statistical Power ◽  
Parametric Model ◽  
Semiparametric Models ◽  
Parametric Models ◽  
Large Sample Size ◽  
Low Doses ◽  
P Values ◽  
The Impact

For many dose–response studies, large samples are not available. Particularly, when the outcome of interest is binary rather than continuous, a large sample size is required to provide evidence for hormesis at low doses. In a small or moderate sample, we can gain statistical power by the use of a parametric model. It is an efficient approach when it is correctly specified, but it can be misleading otherwise. This research is motivated by the fact that data points at high experimental doses have too much contribution in the hypothesis testing when a parametric model is misspecified. In dose–response analyses, to account for model uncertainty and to reduce the impact of model misspecification, averaging multiple models have been widely discussed in the literature. In this article, we propose to average semiparametric models when we test for hormesis at low doses. We show the different characteristics of averaging parametric models and averaging semiparametric models by simulation. We apply the proposed method to real data, and we show that P values from averaged semiparametric models are more credible than P values from averaged parametric methods. When the true dose–response relationship does not follow a parametric assumption, the proposed method can be an alternative robust approach.

scholarly journals Impact of Abstinence and of Reducing Illicit Drug Use Without Abstinence on Human Immunodeficiency Virus Viral Load

2019 ◽  
Vol 70 (5) ◽  
pp. 867-874 ◽  
Author(s):  
Robin M Nance ◽  
Maria Esther Perez Trejo ◽  
Bridget M Whitney ◽  
Joseph A C Delaney ◽  
Fredrick L Altice ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Substance Use ◽  
Viral Load ◽  
Drug Use ◽  
Viral Suppression ◽  
Illicit Drug ◽  
Illicit Drug Use ◽  
Hiv Viral Load ◽  
Immunodeficiency Virus ◽  
The Impact

Abstract Background Substance use is common among people living with human immunodeficiency virus (PLWH) and a barrier to achieving viral suppression. Among PLWH who report illicit drug use, we evaluated associations between HIV viral load (VL) and reduced use of illicit opioids, methamphetamine/crystal, cocaine/crack, and marijuana, regardless of whether or not abstinence was achieved. Methods This was a longitudinal cohort study of PLWH from 7 HIV clinics or 4 clinical studies. We used joint longitudinal and survival models to examine the impact of decreasing drug use and of abstinence for each drug on viral suppression. We repeated analyses using linear mixed models to examine associations between change in frequency of drug use and VL. Results The number of PLWH who were using each drug at baseline ranged from n = 568 (illicit opioids) to n = 4272 (marijuana). Abstinence was associated with higher odds of viral suppression (odds ratio [OR], 1.4–2.2) and lower relative VL (ranging from 21% to 42% by drug) for all 4 drug categories. Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with VL suppression (OR, 2.2, 1.6, respectively). Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with lower relative VL (47%, 38%, respectively). Conclusions Abstinence was associated with viral suppression. In addition, reducing use of illicit opioids or methamphetamine/crystal, even without abstinence, was also associated with viral suppression. Our findings highlight the impact of reducing substance use, even when abstinence is not achieved, and the potential benefits of medications, behavioral interventions, and harm-reduction interventions.

scholarly journals Rate of CD4+Cell Count Increase over Periods of Viral Load Suppression: Relationship with the Number of Previous Virological Failures

2010 ◽  
Vol 51 (4) ◽  
pp. 456-464 ◽  
Author(s):  
Maria Paola Trotta ◽  
Alessandro Cozzi‐Lepri ◽  
Adriana Ammassari ◽  
Jacopo Vecchiet ◽  
Giovanni Cassola ◽  
...  
Keyword(s):  
Viral Load ◽  
Cell Count ◽  
Viral Load Suppression ◽  
Cd4 Cell Count ◽  
Cd4 Cell ◽  
Cell Count Increase

scholarly journals HEALTH TRAJECTORIES OVER TIME IN THE ATHLOS PROJECT: FINDINGS FROM MULTIPLE COHORTS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S798-S798
Author(s):  
Matthew Prina
Keyword(s):  
Physical Activity ◽  
Alcohol Consumption ◽  
Cohort Studies ◽  
Healthy Ageing ◽  
The Third ◽  
Health Trajectories ◽  
Working Together ◽  
The Impact ◽  
Over Time

Abstract The ATHLOS (Ageing Trajectories of Health: Longitudinal Opportunities and Synergies) project is a consortium of 15 partners across Europe who are working together to understand patterns of healthy ageing trajectories, and to seek the factors that determine those patterns, in a harmonised dataset of 17 international cohort studies of ageing. During this symposium we will be presenting some of the work that has recently been carried out within this project. The symposium will consist of four talks: the first talk will introduce the project, and describe the preliminary work that took place within the first few years of the project, and the challenges faced by the consortium. The second talk will focus on the harmonisation process and on the development of the health metric, an indicator used to measure healthy ageing in this project. The third talk will focus on inequalities in healthy ageing, specifically investigating the impact of education and wealth across cohorts. Finally, in the last talk we will describe the role of lifestyle behaviours (specifically physical activity, smoking and alcohol consumption) and their impact on healthy ageing trajectories.

The Impact of Delayed Hepatitis C Viral Load Suppression on Patient Risk: Historical Evidence from the Veterans Administration

2016 ◽  
Vol 19 (2) ◽  
pp. 333-351 ◽  
Author(s):  
Tara Matsuda ◽  
Jeffrey S. McCombs ◽  
Ivy Tonnu-Mihara ◽  
Justin McGinnis ◽  
D. Steven Fox
Keyword(s):  
Viral Load ◽  
Hepatitis C ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Viral Load Suppression ◽  
Clinical Registry ◽  
Patient Risk ◽  
Viral Response ◽  
Clinical Events ◽  
The Impact

Abstract Background: The high cost of new hepatitis C (HCV) treatments has resulted in “watchful waiting” strategies being developed to safely delay treatment, which will in turn delay viral load suppression (VLS). Objective: To document if delayed VLS adversely impacted patient risk for adverse events and death. Methods: 187,860 patients were selected from the Veterans Administration’s (VA) clinical registry (CCR), a longitudinal compilation of electronic medical records (EMR) data for 1999–2010. Inclusion criteria required at least 6 months of CCR/EMR data prior to their HCV diagnosis and sufficient data post-diagnosis to calculate one or more FIB-4 scores. Primary outcome measures were time-to-death and time-to-a composite of liver-related clinical events. Cox proportional hazards models were estimated separately using three critical FIB-4 levels to define early and late viral response. Results: Achieving an undetectable viral load before the patient’s FIB-4 level exceed pre-specified critical values (1.00, 1.45 and 3.25) effectively reduced the risk of an adverse clinical events by 33–35% and death by 21–26%. However, achieving VLS after FIB-4 exceeds 3.25 significantly reduced the benefit of viral response. Conclusions: Delaying VLS until FIB-4 >3.25 reduces the benefits of VLS in reducing patient risk.

scholarly journals Impact of stressful death or divorce in people with HIV: A prospective examination and the buffering effects of religious coping and social support

2017 ◽  
Vol 25 (5) ◽  
pp. 606-616 ◽  
Author(s):  
Gail Ironson ◽  
Sarah M Henry ◽  
Brian D Gonzalez
Keyword(s):  
Social Support ◽  
Viral Load ◽  
Religious Coping ◽  
Elevated Risk ◽  
The Impact ◽  
Over Time ◽  
Buffering Effects

This study examined the impact of a stressful death/divorce on psychological and immune outcomes in people with HIV. People with HIV with stressful death/divorce were examined from before the event to up to 12 months later ( n = 45); controls were assessed at similar intervals ( n = 112). Stressful deaths/divorces were associated with increased viral load and anxiety over time ( ps ≤ .014), but not CD4+ or depression. Increased use of religious coping after the stressful death/divorce was associated with slower increases in viral load ( p = .010). These data suggest people with HIV should consider the potentially elevated risk of transmission after such events and seek appropriate monitoring and care.

scholarly journals Vehicle and Fleet Random Effects in a Model of Insurance Rating for Fleets of Vehicles

2006 ◽  
Vol 36 (01) ◽  
pp. 25-77 ◽  
Author(s):  
Jean-François Angers ◽  
Denise Desjardins ◽  
Georges Dionne ◽  
François Guertin
Keyword(s):  
Road Safety ◽  
Parametric Model ◽  
Automobile Insurance ◽  
Vehicle Accidents ◽  
The Road ◽  
Semiparametric Approach ◽  
Safety Code ◽  
Proposed Model ◽  
The Impact ◽  
Over Time

We are proposing a parametric model to rate insurance for vehicles belonging to a fleet. The tables of premiums presented take into account past vehicle accidents, observable characteristics of the vehicles and fleets, and violations of the road-safety code committed by drivers and carriers. The premiums are also adjusted according to accidents accumulated by the fleets over time. The proposed model accounts directly for explicit changes in the various components of the probability of accidents. It represents an extension of bonus malus-type automobile insurance models for individual premiums (Lemaire, 1985; Dionne and Vanasse, 1989 and 1992; Pinquet, 1997 and 1998; Frangos and Vrontos, 2001; Purcaru and Denuit, 2003). The extension adds a fleet effect to the vehicle effect so as to account for the impact that the unobservable characteristics or actions of carriers can have on truck accident rates. This form of rating makes it possible to visualize what impact the behaviors of owners and drivers can have on the predicted rate of accidents and, consequently, on premiums. The results are compared to those of the semiparametric approach.

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