Modelling the association between adherence and viral load in HIV-infected patients

Abstract

The primary objective of this paper is to investigate the effect of adherence to prescribed antiretroviral therapy on virologic response measured repeatedly over time in HIV-infected patients. To this end observations on plasma viral load (HIV RNA) assessed in copies/ml are categorized into four clinically meaningful states, [0--50[, [50--400[, [400--2000[, [2000 and up. A time-dependent continuation ratio model is used to analyse longitudinal ordinal responses. The main challenge lies in modelling dependencies over time and using information contained in the data efficiently to establish a dynamic relation between observed patient adherence and viral load. Among the several measures of adherence investigated, two specifically account for long periods of time without intake. One is derived from the third moment of the inter-dose interval distribution, while the second reflects internal drug exposure using pharmacokinetic parameters. The approach is applied to a clinical trial involving 35 patients who were followed over 12 months. Results demonstrate a significant relation between patient adherence and virologic response.

Antiepileptic drug nonadherence predicts pediatric epilepsy seizure outcomes

“…First, the relationship between nonadherence to AEDs and seizure outcomes is not linear, as it is with other chronic conditions (e.g., diabetes, hypertension, HIV). [17][18][19] However, these data suggest that patients in the moderate and variable nonadherence groups could benefit from adherence promotion interventions early in the epilepsy course that are geared to the family's specific adherence barriers, which were not examined in this study. Several empirically supported adherence interventions (e.g., multimodal interventions involving education, organization strategies, and problem-solving) have been developed for pediatric chronic conditions.…”

Modeling Virologic Response in HIV-1 Infected Patients to Assess Medication Adherence

“…Several studies investigated the association between virologic responses and adherence assessed by MEMS data only without considering other confounding factors such as drug resistance using standard modeling methods including Poisson regression (Knafl et al, 2004), logistic regression (Vrijens et al, 2005) and linear mixed-effects model (Liu et al, 2007). In this article, we developed a mechanism-based nonlinear time-varying differential equation model for long-term dynamics to (i) establish the relationship of virologic response (viral load trajectory) with drug adherence and drug resistance, (ii) to describe both suppression and resurgence of virus, (iii) to directly incorporate observed drug adherence and susceptibility into a function of treatment efficacy and (iv) to use a hierarchical Bayesian mixed-effects modeling approach that can not only combine prior information with current clinical data for estimating dynamic parameters, but also characterize inter-subject variability.…”

“…It has been argued that this is not a good adherence measure because other factors may influence viral load (pharmacokinetics, drug resistance etc.). However, there is a tight correlation between viral load and adherence (Haubrich et al, 1999;Paterson et al, 2000), but results vary by adherence method and summary adherence statistic (Vrijens & Goetghebeur, 1997;Vrijens et al, 2005) . Several recent papers explore the methodological and operational issues when evaluating electronic drug monitoring adherence on viral load (Arnsten et al, 2001b;Fennie et al, 2006;Fletcher et al, 2005;Llabre et al, 2006;Liu et al , 2006;Liu et al , 2007;Pearson et al , 2007;Vrijens et al, 2005).…”

Adherence Profiles and Therapeutic Responses of Treatment-Naive HIV-Infected Patients Starting Boosted Atazanavir-Based Therapy in the ANRS 134-COPHAR 3 Trial

“…The agreement between the methods for discriminating adherence of Ͼ95% during similar periods was calculated using Cohen's kappa coefficient. The longitudinal data with repeated measurements were analyzed using generalized linear mixed models (22,23). For the continuous outcomes, such as adherence, we used the MIXED procedure in SAS with the same 5 periods defined for DVS.…”