Abstract
BackgroundSuccessful 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.Presentation of the hypothesisWith 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.Testing the hypothesisSpikes 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.Implications of the hypothesisIt 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.
Highlights
Successful treatment of HIV-positive patients is fundamental to controlling the progression to AIDS
Whilst the first cases of AIDS were identified in the USA [1,2], and shortly after in Europe [3,4] it is known that the disease originated from sub-Saharan Africa [5], which currently holds two thirds of the world's 33.2 million people living with HIV
A recent analysis showed that life expectancy at age 20 years had increased by over 13 years since the introduction of combination antiretroviral therapy and currently life expectancy of HIV patients at age 20 is up to two thirds that of the general non-HIV population [9]
Summary
Whilst the first cases of AIDS were identified in the USA [1,2], and shortly after in Europe [3,4] it is known that the disease originated from sub-Saharan Africa [5], which currently holds two thirds of the world's 33.2 million people living with HIV. Whilst clearly preliminary work to validate this hypothesis needs to be undertaken, if validated the information gained could be used to corroborate and clarify verbal adherence discussions between patients and care-providers, enabling care-providers to recognise adherence problems more accurately and identify opportunities to provide appropriate (re-) education, assistance or regimen change, to minimise disease progression If established, this approach will clearly allow for the level of adherence to drug therapy regimes to be monitored. The utilisation of VL data, with knowledge of the presence (or lack) of drug resistant mutations, should allow clinicians to form a more accurate picture of the adherence levels of their patients This will allow treatment change events and clinical management alterations to be made that may prevent or reduce the occurrence of patient non-adherence to the therapeutic regime. This latter approach would directly help clinicians to differentiate between non-responding and non-adherent patients
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