Abstract
BackgroundEstimates of the prevalence of transmitted HIV drug resistance (TDR) in a population are derived from resistance tests performed on samples from patients thought to be naïve to antiretroviral treatment (ART). Much of the debate over reliability of estimates of the prevalence of TDR has focused on whether the sample population is representative. However estimates of the prevalence of TDR will also be distorted if some ART-experienced patients are misclassified as ART-naïve.MethodsThe impact of misclassification bias on the rate of TDR was examined. We developed methods to obtain adjusted estimates of the prevalence of TDR for different misclassification rates, and conducted sensitivity analyses of trends in the prevalence of TDR over time using data from the UK HIV Drug Resistance Database. Logistic regression was used to examine trends in the prevalence of TDR over time.ResultsThe observed rate of TDR was higher than true TDR when misclassification was present and increased as the proportion of misclassification increased. As the number of naïve patients with a resistance test relative to the number of experienced patients with a test increased, the difference between true and observed TDR decreased. The observed prevalence of TDR in the UK reached a peak of 11.3% in 2002 (odds of TDR increased by 1.10 (95% CI 1.02, 1.19, p(linear trend) = 0.02) per year 1997-2002) before decreasing to 7.0% in 2007 (odds of TDR decreased by 0.90 (95% CI 0.87, 0.94, p(linear trend) < 0.001) per year 2002-2007. Trends in adjusted TDR were altered as the misclassification rate increased; the significant downward trend between 2002-2007 was lost when the misclassification increased to over 4%.ConclusionThe effect of misclassification of ART on estimates of the prevalence of TDR may be appreciable, and depends on the number of naïve tests relative to the number of experienced tests. Researchers can examine the effect of ART misclassification on their estimates of the prevalence of TDR if such a bias is suspected.
Highlights
Estimates of the prevalence of transmitted HIV drug resistance (TDR) in a population are derived from resistance tests performed on samples from patients thought to be naïve to antiretroviral treatment (ART)
Adjusted estimates of the prevalence of TDR In practice, the misclassification rate in a surveillance population is unknown and estimates of the prevalence of TDR are based on patients classified as ART-naïve
Empirical adjustment of the prevalence of TDR to account for the effect of misclassification of treatment status: the trend over time in the UK The observed prevalence of TDR in the UK reached a peak of 11.3% in 2002 (odds of TDR increased by 1.10 (95% CI 1.02, 1.19, p(linear trend) = 0.02) per year 19972002) before decreasing to 7.0% in 2007 (odds of TDR decreased by 0.90 (95% CI 0.87, 0.94, p(linear trend) < 0.001) per year 2002-2007) (Figure 2)
Summary
Estimates of the prevalence of TDR will be distorted if some ARTexperienced patients are misclassified as ART-naïve. Estimates of the prevalence of transmitted HIV drug resistance (TDR) in a population are derived from resistance tests performed on samples from patients thought to be naïve to antiretroviral treatment (ART). The certainty of whether a patient is naïve to treatment at the time a sample for resistance testing is taken relies on sources of information about a patient’s treatment status. In this paper we quantify the potential extent of this bias and its impact on estimates of the prevalence of TDR, illustrate methods to obtain adjusted estimates of the prevalence of TDR under different assumptions of the rate of misclassification, and conduct sensitivity analyses of trends in the prevalence of TDR over time using data from the UK HIV Drug Resistance Database
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