Transmembrane protein polymorphisms and resistance to T-20 (Enfuvirtide, Fuzeon®) in HIV-1 infected therapy-naive seroconverters and AIDS patients under HAART-T-20 therapy

Several large studies in Europe and the USA revealed that approximately 10% of all newly diagnosed patients harbour HIV-1 variants with at least one major resistance-associated mutation. In this review we discuss the underlying mechanisms that drive the evolution of drug-resistant viruses after transmission to the new host. In a comprehensive literature search 12 papers describing the evolution of 58 cases of transmitted resistant HIV-1 variants were found. Based on observations in the literature we propose three pathways describing the evolution of resistant HIV-1 after transmission to a new host. Firstly, reversion of the resistance mutation towards wild-type may rapidly occur when drug resistance mutations severely impact replicative capacity. Alternatively, a second pathway involves replacement of transmitted drug resistance mutations by atypical amino acids that also improve viral replication capacity. In the third evolutionary pathway the resistance mutations persist either because they do not significantly affect viral replication capacity or evolution is constrained by fixation through compensatory mutations. In the near future ultra-sensitive resistance tests may provide more insight into the presence of archived and minority variants and their clinical relevance. Meanwhile, clinical guidelines advise population sequence analysis of the baseline plasma sample to identify transmission of resistance. Given the limited sensitivity of this technique for minority populations and the delay between the moment of infection and time of analysis, knowledge of the described evolutionary mechanisms of transmitted drug resistance patterns is essential for clinical management and public health strategies.

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“…Two groups reported transmission of viruses with resistance mutations to the fusion inhibitor enfuvirtide. 40,41 However,…”

Section: Resultsmentioning

confidence: 99%

Evolutionary pathways of transmitted drug-resistant HIV-1

Pingen

Nijhuis

Bruijn

et al. 2011

Journal of Antimicrobial Chemotherapy

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“…In particular, the conserved FLGFL motif at positions 8-12 has been reported to be essential for fusogenic activities (5). Recent studies have shown that mutations with a polar residue inserted into this motif, such as V2E and L9R substitutions, reduced its fusogenic activity significantly (6). …”

mentioning

confidence: 99%

Characterization of Gp41 Polymorphisms in the Fusion Peptide Domain and T-20 (Enfuvirtide) Resistance-Associated Regions in Korean HIV-1 Isolates

et al. 2014

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HIV-1 gp41 is an envelope protein that plays an essential role in virus entry. The mutation of gp41 affects HIV-1 entry and susceptibility to the fusion inhibitor T-20. Therefore, we analyzed the natural polymorphism of gp41 of 163 HIV-1 isolates from T-20-naïve Koreans infected with HIV-1. This study of gp41 polymorphisms showed that insertions in the fourth threonine (74.8%) and L7M substitutions (85.3%) were more frequent in the fusion peptide motif in Korean HIV-1 isolates compared with those from other countries. Minor T-20 resistance mutations such as L45M (1.2%), N126K (1.2%), and E137K (6.7%) were detected, but the critical T-20 resistance mutations were not detected in the gp41 HR1 and HR2 regions. In addition, the N42S mutation (12.9%) associated with T-20 hypersusceptibility was detected at a high frequency. These results may serve as useful data for studies considering T-20 for use in the development of a more effective anti-retroviral treatment in Korea.Graphical Abstract

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“…Fourthly, in the recent years, considerable numbers of peptide drugs have been approved or are under clinical studies for a wide variety of diseases such as AIDS and other malignancies. Several selected successful therapeutic peptides isolated from phage display, which have been approved or are under clinical studies, are listed along with their functions, indications, and manufacturers .…”

Section: Applications Of Bacteriophagesmentioning

confidence: 99%

Bacteriophages: an overview of the control strategies against multiple bacterial infections in different fields

et al. 2018

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Bacteriophages (phages/viruses) need host bacteria to replicate and propagate.Primarily, a bacteriophage contains a head/capsid to encapsidate the genetic material. Some phages contain tails. Phages encode endolysins to hydrolyze bacterial cell wall.The two main classes of phages are lytic or virulent and lysogenic or temperate. In comparison with antibiotics, to deal with bacterial infections, phage therapy is thought to be more effective. In 1921, the use of phages against bacterial infections was first demonstrated. Later on, in humans, phage therapy was used to treat skin infections caused by Pseudomonas species. Furthermore, phages were successfully employed against infections in animalscalves, lambs, and pigs infected with Escherichia coli. In agriculture, for instance, phages have successfully been used e.g., Apple blossom infection, caused by Erwinia amylovora, was effectively catered with the use of bacteriophages. Bacteriophages were also used to control E. coli, Salmonella, Listeria, and Campylobacter contamination in food. Comparatively, phage display is a recently discovered technology, whereby, bacteriophages play a significant role. This review is an effort to collect almost recent and relevant information regarding applications and complications associated with the use of bacteriophages.

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Transmembrane protein polymorphisms and resistance to T-20 (Enfuvirtide, Fuzeon®) in HIV-1 infected therapy-naive seroconverters and AIDS patients under HAART-T-20 therapy

Cited by 14 publications

References 26 publications

Evolutionary pathways of transmitted drug-resistant HIV-1

Evolutionary pathways of transmitted drug-resistant HIV-1

Characterization of Gp41 Polymorphisms in the Fusion Peptide Domain and T-20 (Enfuvirtide) Resistance-Associated Regions in Korean HIV-1 Isolates

Bacteriophages: an overview of the control strategies against multiple bacterial infections in different fields

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