Assessment of HIV molecular surveillance capacity in the European Union, 2016

Keating, Patrick; Pharris, Anastasia; Leitmeyer, Katrin; Angelis, Stefania De; Wensing, Annemarie M. J.; Amato‐Gauci, Andrew J.; Broberg, Eeva

doi:10.2807/1560-7917.es.2017.22.49.17-00269

Cited by 6 publications

(4 citation statements)

References 14 publications

(16 reference statements)

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“…It has also been suggested that the increased use of Pre-exposure prophylaxis among people at risk for HIV infection makes it even more important to continuously monitor TDRM and transmission trends to ensure the sustainability of this intervention method [30]. In order to better inform and maintain treatment regimens, the European Centre for Disease Prevention and Control is currently evaluating the capacity for HIV molecular surveillance within the European Union and European Economic Area [31,32].…”

Section: Resultsmentioning

confidence: 99%

Characterisation of HIV-1 transmission clusters and drug-resistant mutations in Denmark, 2004 to 2016

et al. 2018

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This study describes the prevalence of human immunodeficiency virus (HIV) drug resistance mutations among 1,815 patients in Denmark from 2004 to 2016 and characterises transmission clusters. POL sequences were analysed for subtype, drug resistance mutations and phylogenetic relationship. The prevalence of surveillance drug resistance mutations (SDRM) was 6.7%, while the prevalence of drug resistance mutations (DRM) with a clinical impact was 12.3%. We identified 197 transmission clusters with 706 patients. Patients 40 years or older were less likely to be members of a transmission cluster and patients in transmission clusters were less likely to be infected abroad. The proportion of late presenters (LP) was lower in active compared with inactive clusters. Large active clusters consisted of more men who have sex with men (MSM), had members more frequently infected in Denmark and contained a significantly lower proportion of LP and significantly fewer patients with DRM than small active clusters. Subtyping demonstrated that the Danish HIV epidemic is gradually becoming more composed of non-B subtypes/circulating recombinant forms. This study shows that active HIV-1 transmission has become increasingly MSM-dominated and that the recent increase in SDRM and DRM prevalence is not associated with more sustained transmission within identified transmission networks or clusters.

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Section: Resultsmentioning

confidence: 99%

Characterisation of HIV-1 transmission clusters and drug-resistant mutations in Denmark, 2004 to 2016

et al. 2018

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“…Molecular markers of OXA-R now allow efficient monitoring of the distribution of OXA-R alleles in schistosome populations. This approach is widely used for other parasites and pathogens such as malaria parasite [46] and HIV [47]. For schistosome, collections such as SCAN which contain thousands of parasite samples from multiple locations [17] will be extremely valuable for this work: regular sampling in different endemic regions will help to update the resistance landscape.…”

Section: Discussionmentioning

confidence: 99%

Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

et al. 2019

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Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29–14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate OXA deployment. We conclude that standing variation for OXA resistance is widespread in S. mansoni.

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“…A recent survey within the European HIV surveillance network revealed that some countries publish their national HIVDR data in surveillance reports or in scientific publications [6]. However, it also indicated that countries use different methods to define and select study populations and this may complicate the interpretation and comparison of national HIVDR prevalence data.…”

Section: Introductionmentioning

confidence: 99%

Piloting a surveillance system for HIV drug resistance in the European Union

Laar¹,

Bosman²,

Pharris

et al. 2019

Eurosurveillance

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Background A steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential. Aim We piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level. Method All 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance. Results Nine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34). Conclusion We conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information.

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Assessment of HIV molecular surveillance capacity in the European Union, 2016

Cited by 6 publications

References 14 publications

Characterisation of HIV-1 transmission clusters and drug-resistant mutations in Denmark, 2004 to 2016

Characterisation of HIV-1 transmission clusters and drug-resistant mutations in Denmark, 2004 to 2016

Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

Piloting a surveillance system for HIV drug resistance in the European Union

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