We chose to include the TLVOR algorithm (definition 1) because it is commonly used in clinical trials. We also included the second definition because virological failure (excluding treatment Idasanutlin mouse changes because of side effects) leads to resistance mutations which correlate with poor prognosis [7,8] and reduce future treatment options. Also, the development of a viral load of >400 copies/mL on treatment may reflect
poor adherence to treatment, which may in turn reflect suboptimal clinical care. In definition 2, changing treatment because of side effects, patient preference for once-daily therapy or other reasons not associated with a detectable viral load was not deemed to be failure, because this was unlikely to lead to the development of resistance.
In definition 3, we included patients as having experienced failure if they stopped any treatment for longer than 6 months, because studies have shown that individuals who stop treatment for longer than 6 months have worse outcomes than those who remain on treatment . We then compared the three definitions of failure using Kaplan–Meier survival analyses over the study period. In addition, we compared each of the three definitions against itself for two time periods, the first time period being January 2000 to June 2004 and the second being July 2004 to December 2008, to determine if there were significant changes between these periods for the different definitions. Finally, we examined how closely each of these three definitions of treatment failure correlated with the requirements of quality outcome measures. These include: the ease and feasibility of collection of the outcome, the degree to buy ICG-001 which the outcomes are correlated with the clinical prognosis, the degree to which the outcomes are predicted by differences in the provider characteristics rather than differences among individual patients, the frequency with which an event occurs, and finally the need for risk adjustment before the results can be interpreted [3,4]. Viral load measurements were performed at the Victorian Infectious Diseases Laboratory (VIDRL) using the Roche Amplicor HIV Monitor Version 1.5 (Roche
Molecular Diagnostics, Pleasanton, California, USA) UltraSensitive assay for measurement of viral RNA. T-cell lymphocytes (CD4) were measured using flow cytometry. Each endpoint was analysed Thalidomide using a Kaplan–Meier survival analysis in spss version 17 (SPSS Inc., Chicago, IL, USA). Individuals who had not reached an endpoint by the time of their last viral load measurement were censored. Log rank (Mantel–Cox) χ2 was used to determine the significance of differences between definitions and between the two time periods for the same definition. There were 310 patients who commenced highly active antiretroviral therapy (HAART) for the first time during the study period. Of these, 268 were male, 41 were female and one was transgender. The median age of the patients was 34 (range 25–70) years. Only 19 (6%) were injecting drug users.