• HIV-1 subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics

      Abecasis, Ana B; Wensing, Annemarie MJ; Paraskevis, Dimitris; Vercauteren, Jurgen; Theys, Kristof; Van de Vijver, David AMC; Albert, Jan; Asjö, Birgitta; Balotta, Claudia; Beshkov, Danail; Camacho, Ricardo J; Clotet, Bonaventura; De Gascun, Cillian; Griskevicius, Algis; Grossman, Zehava; Hamouda, Osamah; Horban, Andrzej; Kolupajeva, Tatjana; Korn, Klaus; Kostrikis, Leon G; Kücherer, Claudia; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Schmit, Jean-Claude; Sönnerborg, Anders; Stanekova, Danika; Stanojevic, Maja; Struck, Daniel; Boucher, Charles AB; Vandamme, Anne-Mieke (2013-01-14)
      Abstract Background Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes. Results We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02_AG (4.7%). Substantial differences in the proportion of new diagnoses with distinct subtypes were found between European countries: the lowest proportion of subtype B was found in Israel (27.9%) and Portugal (39.2%), while the highest was observed in Poland (96.2%) and Slovenia (93.6%). Other subtypes were significantly more diagnosed in immigrant populations. Subtype B was significantly more diagnosed in men than in women and in MSM > IDUs > heterosexuals. Furthermore, the subtype distribution according to continent of origin of the patients suggests they acquired their infection there or in Europe from compatriots. Conclusions The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients.
    • Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

      Frentz, Dineke; Van de Vijver, David AMC; Abecasis, Ana B; Albert, Jan; Hamouda, Osamah; Jørgensen, Louise B; Kücherer, Claudia; Struck, Daniel; Schmit, Jean-Claude; Vercauteren, Jurgen; Åsjö, Birgitta; Balotta, Claudia; Beshkov, Danail; Camacho, Ricardo J; Clotet, Bonaventura; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzej; Kolupajeva, Tatjana; Korn, Klaus; Kostrikis, Leondios G; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Stanekova, Danica; Stanojevic, Maja; Van Wijngaerden, Eric; Wensing, Annemarie MJ; Boucher, Charles AB; on behalf of the SPREAD Programme (2014-07-21)
      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.
    • Limited cross-border infections in patients newly diagnosed with HIV in Europe

      Frentz, Dineke; Wensing, Annemarie M J; Albert, Jan; Paraskevis, Dimitrios; Abecasis, Ana B; Hamouda, Osamah; Jørgensen, Louise B; Kücherer, Claudia; Struck, Daniel; Schmit, Jean-Claude; Åsjö, Birgitta; Balotta, Claudia; Beshkov, Danail; Camacho, Ricardo J; Clotet, Bonaventura; Coughlan, Suzie; De Wit, Stéphane; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzej; Kolupajeva, Tatjana; Korn, Klaus; Kostrikis, Leondios G; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Otelea, Dan; Paredes, Roger; Poljak, Mario; Puchhammer-Stöckl, Elisabeth; Sönnerborg, Anders; Stanekova, Danica; Stanojevic, Maja; Vandamme, Anne-Mieke; Boucher, Charles A B; Van de Vijver, David A M C; SPREAD Programme (2013-04-03)
      Abstract Background International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe. Results Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002–2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value <0.0001), in men who have sex with men (P-value <0.0001), and in recently infected patients (P-value =0.045). Conclusions Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics.