High prevalence of bevirimat resistance mutations in protease inhibitor-resistant HIV isolates

AIDS ◽  
2010 ◽  
Vol 24 (5) ◽  
pp. 669-673 ◽  
Author(s):  
Jens Verheyen ◽  
Chris Verhofstede ◽  
Elena Knops ◽  
Linos Vandekerckhove ◽  
Axel Fun ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Resistance Mutations ◽  
High Prevalence

scholarly journals HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting

2019 ◽  
Vol 18 ◽  
pp. 232595821984906
Author(s):  
Nawaid Hussain Khan ◽  
Mikashmi Kohli ◽  
Kartik Gupta ◽  
Bimal Kumar Das ◽  
Ravindra Mohan Pandey ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
First Line Therapy ◽  
Resource Limited ◽  
High Prevalence ◽  
Hiv 1 ◽  
Limited Setting

Introduction: The present study aimed to report the prevalent HIV-1 drug-resistant mutations in patients with HIV-1 alone and tuberculosis (TB) coinfection alone to improve our understanding of the mutation patterns and aid treatment decisions. Methods: Patients with HIV-1 and HIV-TB on treatment for more than 1 year with suspected failure were recruited. Sequencing of protease and two-thirds of the region of reverse transcriptase gene was done for drug-resistant mutations. Results: In the HIV-TB group (n = 25), 88%, 92%, and 12% had mutations to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs), respectively. In the HIV-alone group (n = 25), 84%, 100%, and 4% had mutations to NRTIs, NNRTIs, and PIs, respectively. M184V, M41L, D67N, G190A, A98G, and K103N were the most common mutations seen. Conclusion: There is a high prevalence of drug-resistant mutations in HIV and HIV-TB coinfected patients.

scholarly journals Low Levels of Pyrethroid Resistance in Hybrid Offspring of a Highly Resistant and a More Susceptible Mosquito Strain

2020 ◽  
Vol 20 (4) ◽  
Author(s):  
Matthew Pinch ◽  
Stacy D Rodriguez ◽  
Soumi Mitra ◽  
Yashoda Kandel ◽  
Emily Moore ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Pyrethroid Resistance ◽  
Resistance Mutations ◽  
Human Host ◽  
High Prevalence ◽  
Rapid Spread ◽  
Choice Assay ◽  
Low Levels ◽  
Control Disease ◽  
Different Strains

Abstract The use of insecticides has been a central approach to control disease-transmitting mosquitoes for the last century. The high prevalence of pyrethroid use as public health insecticides has resulted in the evolution of pyrethroid resistance in many populations of Aedes aegypti (Linnaeus) (Diptera: Culicidae), throughout its global distribution range. Insecticide resistance is often correlated with an associated fitness cost. In this project, we studied the phenotypes of hybrid mosquitoes derived from crossing a pyrethroid-resistant strain of Ae. aegypti (Puerto Rico [PR]) with a more susceptible one (Rockefeller [ROCK]). We first sequenced and compared the para gene of both original strains. We then crossed males from one strain with females of the other, creating two hybrids (Puertofeller, Rockorico). We used a Y-tube choice assay to measure the attraction of these strains towards a human host. We then compared the levels of pyrethroid resistance in the different strains. We found three known resistance mutations in the para gene sequence of the PR strain. In our attraction assays, PR females showed lower attraction to humans, than the ROCK females. Both hybrid strains showed strong attraction to a human host. In the insecticide resistance bottle assays, both hybrid strains showed marginal increases in resistance to permethrin compared to the more susceptible ROCK strain. These results suggest that hybrids of sensitive and permethrin-resistant mosquitoes have an incremental advantage compared to more susceptible mosquitoes when challenged with permethrin. This explains the rapid spread of permethrin resistance that was observed many times in the field.

scholarly journals Protease Inhibitor Resistance Analysis in the MONARK Trial Comparing First-Line Lopinavir-Ritonavir Monotherapy to Lopinavir-Ritonavir plus Zidovudine and Lamivudine Triple Therapy

2009 ◽  
Vol 53 (7) ◽  
pp. 2934-2939 ◽  
Author(s):  
Constance Delaugerre ◽  
Philippe Flandre ◽  
Marie Laure Chaix ◽  
Jade Ghosn ◽  
François Raffi ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Triple Therapy ◽  
Virological Failure ◽  
Therapy Group ◽  
Resistance Mutation ◽  
Resistance Testing ◽  
Initial Screening ◽  
Resistance Mutations ◽  
Cd4 Cell Count ◽  
Hiv 1

ABSTRACT The MONARK study was a pilot randomized trial comparing the safety and efficacy of lopinavir-ritonavir (LPV/r) monotherapy to those of LPV/r-zidovudine-lamivudine triple therapy for antiretroviral-naïve human immunodeficiency virus type 1 (HIV-1)-infected patients. Resistance testing was performed at the time of initial screening and at the time of virological failure (defined to include low-level viremia with >50 and <400 HIV-1 virus RNA copies/ml of plasma). Changes from the baseline sequences, including mutations noted on the 2008 International AIDS Society—USA list of resistance-associated protease mutations, were considered. Drug resistance testing was performed for 38 patients (5 of 53 on triple therapy and 33 of 83 on monotherapy). By week 96 (W96), virus samples from 18 of 33 patients in the monotherapy arm showed changes from baseline sequences, and 5 of these patients had viruses with major protease inhibitor (PI) resistance-associated mutations (M46I at W40, L76V at W48, M46I and L76V at W48, L10F and V82A at W72, and L76V at W84). Data on virus phenotypes detected at the time of initial screening and the time of virological failure were available for four patients in whom major PI resistance mutations developed, and these data revealed a mean increase of 2.2-fold (range, 0.75- to 4.6-fold) in the LPV 50% inhibitory concentration. All three patients in whom the L76V PI resistance mutation developed were infected with HIV-1 subtype CRF02_AG. In the triple-therapy group, no major PI resistance mutation was selected among the three patients with protease changes by W48. No association between the baseline CD4 cell count and the viral load, the W4 and final viral loads, or the final LPV trough concentration and the emergence of a major PI resistance mutation was found. Major PI resistance-associated mutations were detected in 5 (6%) of 83 patients treated with LPV/r monotherapy, suggesting that LPV/r monotherapy is an inappropriate first option. The mutation L76V may be considered in further studies of lopinavir resistance.

scholarly journals Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients

2019 ◽  
Vol 74 (9) ◽  
pp. 2759-2766 ◽  
Author(s):  
Agustin Resendiz-Sharpe ◽  
Toine Mercier ◽  
Pieter P A Lestrade ◽  
Martha T van der Beek ◽  
Peter A von dem Borne ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Resistance Mutations ◽  
Icu Patients ◽  
High Prevalence ◽  
High Risk Populations ◽  
Haematology Patients ◽  
Culture Positive ◽  
Very High ◽  
Multicentre Cohort ◽  
Overall Mortality

Abstract Background Increasing resistance of Aspergillus fumigatus to triazoles in high-risk populations is a concern. Its impact on mortality is not well understood, but rates from 50% to 100% have been reported. Objectives To determine the prevalence of voriconazole-resistant A. fumigatus invasive aspergillosis (IA) and its associated mortality in a large multicentre cohort of haematology patients with culture-positive IA. Methods We performed a multicentre retrospective study, in which outcomes of culture-positive haematology patients with proven/probable IA were analysed. Patients were stratified based on the voriconazole susceptibility of their isolates (EUCAST broth microdilution test). Mycological and clinical data were compared, along with survival at 6 and 12 weeks. Results We identified 129 A. fumigatus culture-positive proven or probable IA cases; 103 were voriconazole susceptible (79.8%) and 26 were voriconazole resistant (20.2%). All but one resistant case harboured environment-associated resistance mutations in the cyp51A gene: TR34/L98H (13 cases) and TR46/Y121F/T289A (12 cases). Triazole monotherapy was started in 75.0% (97/129) of patients. Mortality at 6 and 12 weeks was higher in voriconazole-resistant cases in all patients (42.3% versus 28.2%, P = 0.20; and 57.7% versus 36.9%, P = 0.064) and in non-ICU patients (36.4% versus 21.6%, P = 0.16; and 54.4% versus 30.7%; P = 0.035), compared with susceptible ones. ICU patient mortality at 6 and 12 weeks was very high regardless of triazole susceptibility (75.0% versus 66.7%, P = 0.99; and 75.0% versus 73.3%, P = 0.99). Conclusions A very high prevalence of voriconazole resistance among culture-positive IA haematology patients was observed. The overall mortality at 12 weeks was significantly higher in non-ICU patients with voriconazole-resistant IA compared with voriconazole-susceptible IA.

Tu1046 Evaluation of the Role of the Immune Responses in Determining the Emergence of HCV Ns3 Resistance Mutations During Protease Inhibitor (PI) Therapy

2015 ◽  
Vol 148 (4) ◽  
pp. S-1095
Author(s):  
Enass A. Abdel-hameed ◽  
Susan D. Rouster ◽  
Hong Ji ◽  
Ashley Ulm ◽  
Helal Hetta ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protease Inhibitor ◽  
Resistance Mutations

scholarly journals Clinically Relevant Interpretation of Genotype and Relationship to Plasma Drug Concentrations for Resistance to Saquinavir-Ritonavir in Human Immunodeficiency Virus Type 1 Protease Inhibitor-Experienced Patients

2004 ◽  
Vol 48 (12) ◽  
pp. 4687-4692 ◽  
Author(s):  
Anne-Geneviève Marcelin ◽  
Cécile Dalban ◽  
Gilles Peytavin ◽  
Claire Lamotte ◽  
Rachid Agher ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Virological Response ◽  
Resistance Index ◽  
Resistance Mutations ◽  
Genotypic Resistance ◽  
Minimum Concentration ◽  
Drug Concentrations ◽  
Immunodeficiency Virus ◽  
Resistance Score

ABSTRACT It has been shown that virological protease inhibitor (PI) resistance mutations present at the initiation of saquinavir (SQV) plus ritonavir (RTV) therapy in PI-experienced patients are the strongest predictors of virological response. But most of the current resistance algorithms are adapted for unboosted SQV regimens. We applied a stepwise methodology for the development and validation of a clinically relevant genotypic resistance score for an SQV (800 mg twice per day [b.i.d.]) plus RTV (100 mg b.i.d.)-containing regimen. PI-experienced patients treated by this regimen achieved a human immunodeficiency virus plasma viral load (VL) of <200 copies/ml at months 3 to 5 for 41.7% of subjects. Adjusted in a multivariate analysis, taking into account all the confounding factors, such as the nucleoside used, five mutations were combined in a resistance score associated with a reduced virological response to an SQV-plus-RTV regimen: L24I, I62V, V82A/F/T/S, I84V, and L90IM. Patients with isolates harboring 0 to 1 mutation among the score achieved −2.20 log10 and −1.23 log10 copies/ml of VL reduction, respectively, while it was −0.27 log10 copies/ml for those with at least two mutations, classifying the isolates as “no evidence of resistance” (0 or 1 mutation) or “resistance ” (≥2 mutations). The minimum concentration in plasma (C min) of SQV alone was not associated with the virological response. However, the combination of the SQV C min and the genotypic score, expressed as the genotypic inhibitory quotient, was predictive of the virological response, suggesting that the interpretation of SQV concentrations in plasma should be done only in the context of the resistance index provided by viral genotype for PI-experienced patients.

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