title: An alternative methodology for the prediction of adherence to anti HIV treatment.
abstract: BACKGROUND
  Successful treatment of HIV-positive patients is fundamental to controlling the progression to AIDS. Causes of treatment failure are either related to drug resistance and/or insufficient drug levels in the blood. Severe side effects, coupled with the intense nature of many regimens, can lead to treatment fatigue and consequently to periodic or permanent non-adherence. Although non-adherence is a recognised problem in HIV treatment, it is still poorly detected in both clinical practice and research and often based on unreliable information such as self-reports, or in a research setting, Medication Events Monitoring System caps or prescription refill rates. To meet the need for having objective information on adherence, we propose a method using viral load and HIV genome sequence data to identify non-adherence amongst patients.
  
  
  OBJECTIVE
  With non-adherence operationally defined as a sharp increase in viral load in the absence of mutation, it is hypothesised that periods of non-adherence can be identified retrospectively based on the observed relationship between changes in viral load and mutation.
  
  
  METHODS
  Spikes in the viral load (VL) can be identified from time periods over which VL rises above the undetectable level to a point at which the VL decreases by a threshold amount. The presence of mutations can be established by comparing each sequence to a reference sequence and by comparing sequences in pairs taken sequentially in time, in order to identify changes within the sequences at or around 'treatment change events'. Observed spikes in VL measurements without mutation in the corresponding sequence data then serve as a proxy indicator of non-adherence.
  
  
  CONCLUSIONS
  It is envisaged that the validation of the hypothesised approach will serve as a first step on the road to clinical practice. The information inferred from clinical data on adherence would be a crucially important feature of treatment prediction tools provided for practitioners to aid daily practice. In addition, distinct characteristics of biological markers routinely used to assess the state of the disease may be identified in the adherent and non-adherent groups. This latter approach would directly help clinicians to differentiate between non-responding and non-adherent patients.
authors.affiliation: School of Life Sciences, Kingston University, Penrhyn Road, Kingston-upon-Thames, KT1 2EE, UK. k05437@kingston.ac.uk
authors.forename: I Richard
authors.initials: IR
authors.lastname: Thompson
authors.forename: Penelope
authors.initials: P
authors.lastname: Bidgood
authors.forename: Andrea
authors.initials: A
authors.lastname: Petróczi
authors.forename: James C W
authors.initials: JC
authors.lastname: Denholm-Price
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fielder