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

Frentz, Dineke; Vijver, David van de; Abecasis, Ana; Albert, Jan; Hamouda, Osamah; Jørgensen, Lars; Kücherer, Claudia; Struck, Daniel; Schmit, Jean-Claude; Vercauteren, Jürgen; Åsjö, Birgitta; Balotta, Claudia; Beshkov, Danail; Camacho, Ricardo Jorge; Clotet, Bonaventura; Coughlan, Suzie; Griskevicius, Algirdas; Grossman, Zehava; Horban, Andrzéj; Kolupajeva, Tatjana; Korn, Klaus; Kostrikis, Leondios G.; Liitsola, Kirsi; Linka, Marek; Nielsen, Claus; Oțelea, Dan; Paraskevis, Dimitrios; Paredes, Roger; Poljak, Mario; Puchhammer‐Stöckl, Elisabeth; Sönnerborg, Anders; Staneková, Danica; Stanojević, Maja; Wijngaerden, Eric Van; Wensing, Annemarie M. J.; Boucher, Charles A.

doi:10.1186/1471-2334-14-407

Cited by 48 publications

(46 citation statements)

References 49 publications

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“…Another situation in which resistance testing should be always performed corresponds to naïve patients before starting antiretroviral treatment. Although transmission of resistant HIV-1 variants is highly variable depending on the countries analyzed, different studies performed in Europe over the last decade suggest a relatively stable general prevalence of 8% to 10% for the transmission of viruses that are resistant to at least one antiretroviral drug [68–70]. Also, drug-resistant HIV-1 minority variants can be transmitted [71,72].…”

Section: Discussionmentioning

confidence: 99%

An Efficient Microarray-Based Genotyping Platform for the Identification of Drug-Resistance Mutations in Majority and Minority Subpopulations of HIV-1 Quasispecies

et al. 2016

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The response of human immunodeficiency virus type 1 (HIV-1) quasispecies to antiretroviral therapy is influenced by the ensemble of mutants that composes the evolving population. Low-abundance subpopulations within HIV-1 quasispecies may determine the viral response to the administered drug combinations. However, routine sequencing assays available to clinical laboratories do not recognize HIV-1 minority variants representing less than 25% of the population. Although several alternative and more sensitive genotyping techniques have been developed, including next-generation sequencing (NGS) methods, they are usually very time consuming, expensive and require highly trained personnel, thus becoming unrealistic approaches in daily clinical practice. Here we describe the development and testing of a HIV-1 genotyping DNA microarray that detects and quantifies, in majority and minority viral subpopulations, relevant mutations and amino acid insertions in 42 codons of the pol gene associated with drug- and multidrug-resistance to protease (PR) and reverse transcriptase (RT) inhibitors. A customized bioinformatics protocol has been implemented to analyze the microarray hybridization data by including a new normalization procedure and a stepwise filtering algorithm, which resulted in the highly accurate (96.33%) detection of positive/negative signals. This microarray has been tested with 57 subtype B HIV-1 clinical samples extracted from multi-treated patients, showing an overall identification of 95.53% and 89.24% of the queried PR and RT codons, respectively, and enough sensitivity to detect minority subpopulations representing as low as 5–10% of the total quasispecies. The developed genotyping platform represents an efficient diagnostic and prognostic tool useful to personalize antiviral treatments in clinical practice.

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Section: Discussionmentioning

confidence: 99%

An Efficient Microarray-Based Genotyping Platform for the Identification of Drug-Resistance Mutations in Majority and Minority Subpopulations of HIV-1 Quasispecies

et al. 2016

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“…[3] Apart from clinical implications of ART resistance, the cost of management increases with the presence of resistance mutations. [4] Given, the elaborate laboratory set up required for antiretroviral (ARV) resistance testing, it is expensive and not easily available to a large proportion of HIV-infected individuals in resource-limited countries such as India.…”

Section: Introductionmentioning

confidence: 99%

A study of antiretroviral resistance patterns in treatment experienced and naive human immunodeficiency virus infected-patients

Harjani

Malkani

2016

Indian J Sex Transm Dis

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Background:About 10% of the patients had surveillance drug-related mutations for nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in an Indian study. It was also reported that resistance was maximum for nucleoside reverse transcriptase inhibitors (NRTIs) and minimum for PIs.Methods:The present study was a cross-sectional assessment of 21 human immunodeficiency virus (HIV)-infected individuals attending a HIV care center in a tertiary care center in Mumbai, Maharashtra, India. All HIV-infected individuals included in the present analysis were tested for CD4 count, viral load, and resistance to antiretrovirals (ARVs).Results:A total of 13 male and 8 female were included in the present analysis. Of these, 18 were treatment naive and three were treatment experienced patients. In treatment-naive patients, the proportion of high-level resistance (HLR) was 2% for NRTIs, 5% for PIs, and 11% for NNRTIs. In treatment-naive patients, high susceptibility was observed for darunavir (89%) followed by lopinavir (72%) and fosamprenavir (67%) among PIs. Similarly, susceptibility was high for NRTIs lamivudine (94%), emtricitabine (94%), and tenofovir (89%). However, we found HLR for nevirapine (39%) even in treatment-naive patients.Conclusions:The proportion of HLR was relatively low for PIs and NRTIs, compared with NNRTIs in treatment-naive patients. We also reported a high correlation in resistance patterns among drugs belonging to the same group. Thus, it may be useful to conduct ARV resistance even in newly infected HIV patients and those receiving medications for the first time.

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“…This is because these partial pol sequences (around 1.3 Kb long) are routinely sequenced for genotypic resistance testing123. Although initially the env gene was considered to present the strongest phylogenetic signal, it was argued that some env fragments were too short and/or variable for a robust analysis4.…”

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confidence: 99%

Using nearly full-genome HIV sequence data improves phylogeny reconstruction in a simulated epidemic

Yebra

Hodcroft

Ragonnet‐Cronin

et al. 2016

Sci Rep

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HIV molecular epidemiology studies analyse viral pol gene sequences due to their availability, but whole genome sequencing allows to use other genes. We aimed to determine what gene(s) provide(s) the best approximation to the real phylogeny by analysing a simulated epidemic (created as part of the PANGEA_HIV project) with a known transmission tree. We sub-sampled a simulated dataset of 4662 sequences into different combinations of genes (gag-pol-env, gag-pol, gag, pol, env and partial pol) and sampling depths (100%, 60%, 20% and 5%), generating 100 replicates for each case. We built maximum-likelihood trees for each combination using RAxML (GTR + Γ), and compared their topologies to the corresponding true tree’s using CompareTree. The accuracy of the trees was significantly proportional to the length of the sequences used, with the gag-pol-env datasets showing the best performance and gag and partial pol sequences showing the worst. The lowest sampling depths (20% and 5%) greatly reduced the accuracy of tree reconstruction and showed high variability among replicates, especially when using the shortest gene datasets. In conclusion, using longer sequences derived from nearly whole genomes will improve the reliability of phylogenetic reconstruction. With low sample coverage, results can be highly variable, particularly when based on short sequences.

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

Cited by 48 publications

References 49 publications

An Efficient Microarray-Based Genotyping Platform for the Identification of Drug-Resistance Mutations in Majority and Minority Subpopulations of HIV-1 Quasispecies

An Efficient Microarray-Based Genotyping Platform for the Identification of Drug-Resistance Mutations in Majority and Minority Subpopulations of HIV-1 Quasispecies

A study of antiretroviral resistance patterns in treatment experienced and naive human immunodeficiency virus infected-patients

Using nearly full-genome HIV sequence data improves phylogeny reconstruction in a simulated epidemic

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