John C Martin Foundation.

Viral sequence classification has wide applications in clinical, epidemiological, structural and functional categorization studies. Most existing approaches rely on an initial alignment step followed by classification based on phylogenetic or statistical algorithms. Here we present an ultrafast alignment-free subtyping tool for human immunodeficiency virus type one (HIV-1) adapted from Prediction by Partial Matching compression. This tool, named COMET, was compared to the widely used phylogeny-based REGA and SCUEAL tools using synthetic and clinical HIV data sets (1 090 698 and 10 625 sequences, respectively). COMET's sensitivity and specificity were comparable to or higher than the two other subtyping tools on both data sets for known subtypes. COMET also excelled in detecting and identifying new recombinant forms, a frequent feature of the HIV epidemic. Runtime comparisons showed that COMET was almost as fast as USEARCH. This study demonstrates the advantages of alignment-free classification of viral sequences, which feature high rates of variation, recombination and insertions/deletions. COMET is free to use via an online interface.

The SPREAD Programme investigated prospectively the time trend from September 2002 through December 2005 of transmitted drug resistance (TDR) among 2793 patients in 20 European countries and in Israel with newly diagnosed human immunodeficiency virus type 1 (HIV-1) infection. The overall prevalence of TDR was 8.4% (225 of 2687 patients; 95% confidence interval [CI], 7.4%-9.5%), the prevalence of nucleoside reverse-transcriptase inhibitor (NRTI) resistance was 4.7% (125 of 2687 patients; 95% CI, 3.9%-5.5%), the prevalence of nonucleoside reverse-transcriptase inhibitor (NNRTI) resistance was 2.3% (62 of 2687 patients; 95% CI, 1.8%-2.9%), and the prevalence of protease inhibitor (PI) resistance was 2.9% (79 of 2687 patients; 95% CI, 2.4%-3.6%). There was no time trend in the overall TDR or in NRTI resistance, but there was a statistically significant decrease in PI resistance (P = .04) and in NNRTI resistance after an initial increase (P = .02). We found that TDR appears to be stabilizing in Europe, consistent with recent reports of decreasing drug resistance and improved viral suppression in patients treated for HIV-1 infection.

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Transmitted human immunodeficiency virus drug resistance in Europe is stable at around 8%. The impact of baseline mutation patterns on susceptibility to antiretroviral drugs should be addressed using clinical guidelines. The impact on baseline susceptibility is largest for nonnucleoside reverse transcriptase inhibitors.