Abstract
BackgroundSeveral decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks.Methodology/Principal FindingsIncluded were 3763 treatment-change episodes (TCEs) for which a HIV-1 genotype was available at the time of changing treatment with at least one follow-up viral load measurement. Genotypic susceptibility scores for the active regimens were calculated using scores defined by each interpretation system. Using logistic regression, we determined the association between the genotypic susceptibility score and proportion of TCEs having an undetectable viral load (<50 copies/ml) at 12 (8–16) weeks (2152 TCEs), 24 (16–32) weeks (2570 TCEs), and 48 (44–52) weeks (1083 TCEs). The Area under the ROC curve was calculated using a 10-fold cross-validation to compare the different interpretation systems regarding the sensitivity and specificity for predicting undetectable viral load. The mean genotypic susceptibility score of the systems was slightly smaller for HIVdb, with 1.92±1.17, compared to Rega and ANRS, with 2.22±1.09 and 2.23±1.05, respectively. However, similar odds ratio's were found for the association between each-unit increase in genotypic susceptibility score and undetectable viral load at week 12; 1.6 [95% confidence interval 1.5–1.7] for HIVdb, 1.7 [1.5–1.8] for ANRS, and 1.7 [1.9–1.6] for Rega. Odds ratio's increased over time, but remained comparable (odds ratio's ranging between 1.9–2.1 at 24 weeks and 1.9–2.2 at 48 weeks). The Area under the curve of the ROC did not differ between the systems at all time points; p = 0.60 at week 12, p = 0.71 at week 24, and p = 0.97 at week 48.Conclusions/SignificanceThree commonly used HIV drug resistance interpretation systems ANRS, Rega and HIVdb predict virological response at 12, 24, and 48 weeks, after change of treatment to the same extent.
Highlights
The effectiveness of antiretroviral therapy has been limited by the development of HIV-1 drug resistance
The complex mutational patterns are difficult to interpret, due to the many different drug resistance mutations [6] and the varying levels of decreased susceptibility of these mutations to different drugs. This led to the development of several interpretation systems [7], which provide rules to help physicians interpret HIV-1 drug resistance genotyping results
3131 patients in our study, of which most were male (73%), most were infected with subtype B viruses (81.9%), and the median age was 39 years
Summary
The effectiveness of antiretroviral therapy has been limited by the development of HIV-1 drug resistance. The complex mutational patterns are difficult to interpret, due to the many different drug resistance mutations [6] and the varying levels of decreased susceptibility of these mutations to different drugs. This led to the development of several interpretation systems [7], which provide rules to help physicians interpret HIV-1 drug resistance genotyping results. ANRS, Stanford HIVdb, and Rega are the three most commonly used and publicly available drug resistance interpretation systems, which are all regularly updated. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford’s HIVdb) to predict virological outcome at 12, 24, and 48 weeks
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