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Clinical Trial
. 2014 Jul 21:14:407.
doi: 10.1186/1471-2334-14-407.

Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

Dineke Frentz, David A M C Van de Vijver, Ana B Abecasis, Jan Albert, Osamah Hamouda, Louise B Jørgensen, Claudia Kücherer, Daniel Struck, Jean-Claude Schmit, Jurgen Vercauteren, Birgitta Åsjö, Claudia Balotta, Danail Beshkov, Ricardo J Camacho, Bonaventura Clotet, Suzie Coughlan, Algirdas Griskevicius, Zehava Grossman, Andrzej Horban, Tatjana Kolupajeva, Klaus Korn, Leondios G Kostrikis, Kirsi Liitsola, Marek Linka, Claus Nielsen, Dan Otelea, Dimitrios Paraskevis, Roger Paredes, Mario Poljak, Elisabeth Puchhammer-Stöckl, Anders Sönnerborg, Danica Stanekova, Maja Stanojevic, Eric Van Wijngaerden, Annemarie M J Wensing, Charles A B Boucher  1 ; SPREAD Programme
Collaborators, Affiliations
Clinical Trial

Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

Dineke Frentz et al. BMC Infect Dis. .

Abstract

Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.

Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.

Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM.

Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring.

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Figures

Figure 1
Figure 1
Smoothed line of prevalence of TDRM in patients diagnosed from 2002 to 2007 at time of sequence sampling. (A) Prevalence of TDRM associated with any of the drug classes (any class), nucleoside reverse-transcriptase inhibitor (NRTI), nonnucleoside reverse-transcriptase inhibitor (NNRTI), and protease inhibitor (PI). (B) Prevalence of mutations associated with nucleoside reverse-transcriptase inhibitors (NRTI), thymidine analogue mutations (TAM) and revertants, and the M184V mutation. The p-values of the time trends are shown. The multivariate time trend analyses did not change the time trend estimates and significance.
Figure 2
Figure 2
The K103N mutation in phylogenetic analyses of HIV-1 subtype B pol sequences. The reliability of tree topologies was assessed by bootstrapping with 1000 replicates. A bootstrap support of 70%, or greater, are shown at nodes on the tree. The source of the data, the country of residence, and the presence of an NNRTI resistance mutation are included in the sequence-label. The 16 square brackets show patients in a phylogenetic cluster with bootstrap support of >70% and a mean genetic distance of <0.03 nucleotide substitutions per site; (●) indicated patients with a K103N mutation; (▲) highlights a reference sequence.
See this image and copyright information in PMC

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