Molecular mechanism of HIV-1 integrase-vDNA interactions and strand transfer inhibitor action: A molecular modeling perspective

2011 ◽  
Vol 33 (5) ◽  
pp. 527-536 ◽  
Author(s):  
Weiwei Xue ◽  
Huanxiang Liu ◽  
Xiaojun Yao
Keyword(s):  
Molecular Modeling ◽  
Molecular Mechanism ◽  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Hiv 1

Transmission of integrase strand-transfer inhibitor multidrug-resistant HIV-1: case report and response to raltegravir-containing antiretroviral therapy

2011 ◽  
Vol 16 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Benjamin Young ◽  
Signe Fransen ◽  
Kenneth S Greenberg ◽  
Amy Thomas ◽  
Sharon Martens ◽  
...  
Keyword(s):  
Case Report ◽  
Antiretroviral Therapy ◽  
Multidrug Resistant ◽  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1

HIV-1 Integrase Diversity and Resistance-Associated Mutations and Polymorphisms Among Integrase Strand Transfer Inhibitor-Naive HIV-1 Patients from Cameroon

2020 ◽  
Vol 36 (5) ◽  
pp. 450-455 ◽  
Author(s):  
Sello Given Mikasi ◽  
Josiah Otwoma Gichana ◽  
Cheri Van der Walt ◽  
Dominik Brado ◽  
Adetayo Emmanuel Obasa ◽  
...  
Keyword(s):  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1

Weight gain in antiretroviral therapy-naive HIV-1-infected patients starting a regimen including an integrase strand transfer inhibitor or darunavir/ritonavir

Infection ◽  
2019 ◽  
Vol 48 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Leonardo Calza ◽  
Vincenzo Colangeli ◽  
Marco Borderi ◽  
Isabella Bon ◽  
Aurora Borioni ◽  
...  
Keyword(s):  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor ◽  
Hiv 1

Prevalence of integrase strand transfer inhibitor resistance mutations in antiretroviral-naive HIV-1-infected individuals in Cameroon

2020 ◽  
Vol 76 (1) ◽  
pp. 124-129
Author(s):  
Benjamin M Wenk ◽  
Herbert A Mbunkah ◽  
Ndi N Nsanwe ◽  
Eyongetah T Mbu ◽  
Lydia M Besong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Universal Primers ◽  
Polymorphism Analysis ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Transfer Inhibitor ◽  
Study Sites ◽  
Inhibitor Resistance ◽  
The Impact ◽  
Hiv 1

Abstract Objectives In Cameroon, the integrase (IN) strand transfer inhibitor (INSTI) dolutegravir was recently introduced for the treatment of HIV-1 infection. Since pretreatment HIV-1 drug resistance can jeopardize the success of ART, and considering the high heterogeneity of circulating HIV-1 subtypes in Cameroon, we investigated the prevalence of pretreatment HIV-1 resistance to INSTIs. Methods Fingerprick dried blood spot samples were collected from 339 newly diagnosed HIV-1-infected individuals between 2015 and 2016 in four hospitals in Cameroon. Universal primers were designed to amplify the HIV-1 IN region from amino acid 1 to 276. Amplicons were sequenced with Illumina next-generation sequencing and analysed with the Polymorphism Analysis Sequencing (PASeq) platform, using the Stanford HIV Drug Resistance Database to interpret HIV-1 drug resistance mutations (DRMs). Results The amplification/sequencing success rate was 75.2% with 255/339 sequences obtained. Applying a cut-off of 1%, major DRMs to INSTIs were detected in 13 (5.1%) individuals, but only 1 individual harboured an INSTI DRM (E92G) at a nucleotide frequency ≥15%. However, 140/255 (54.9%) individuals harboured polymorphic accessory INSTI DRMs, mainly at high frequencies. In line with that observation, HIV-1 subtype diversity among individuals was high. Conclusions Pretreatment HIV-1 resistance to INSTIs was low in the study sites, which supports the use of INSTIs in Cameroon. Nevertheless, further studies are necessary to assess the impact of polymorphic accessory INSTI DRMs on INSTI-based ART regimens.

scholarly journals Impact of Primary Elvitegravir Resistance-Associated Mutations in HIV-1 Integrase on Drug Susceptibility and Viral Replication Fitness

2013 ◽  
Vol 57 (6) ◽  
pp. 2654-2663 ◽  
Author(s):  
Michael E. Abram ◽  
Rebecca M. Hluhanich ◽  
Derrick D. Goodman ◽  
Kristen N. Andreatta ◽  
Nicolas A. Margot ◽  
...  
Keyword(s):  
Viral Replication ◽  
Drug Susceptibility ◽  
Viral Fitness ◽  
Cross Resistance ◽  
Replication Capacity ◽  
Strand Transfer ◽  
Recombinant Viruses ◽  
Transfer Inhibitor ◽  
Replication Fitness ◽  
Hiv 1

ABSTRACTElvitegravir (EVG) is an effective HIV-1 integrase (IN) strand transfer inhibitor (INSTI) in advanced clinical development. Primary INSTI resistance-associated mutations (RAMs) at six IN positions have been identified in HIV-1-infected patients failing EVG-containing regimens in clinical studies: T66I/A/K, E92Q/G, T97A, S147G, Q148R/H/K, and N155H. In this study, the effect of these primary IN mutations, alone and in combination, on susceptibility to the INSTIs EVG, raltegravir (RAL), and dolutegravir (DTG); IN enzyme activities; and viral replication fitness was characterized. Recombinant viruses containing the six most common mutations exhibited a range of reduced EVG susceptibility: 92-fold for Q148R, 30-fold for N155H, 26-fold for E92Q, 10-fold for T66I, 4-fold for S147G, and 2-fold for T97A. Less commonly observed primary IN mutations also showed a range of reduced EVG susceptibilities: 40- to 94-fold for T66K and Q148K and 5- to 10-fold for T66A, E92G, and Q148H. Some primary IN mutations exhibited broad cross-resistance between EVG and RAL (T66K, E92Q, Q148R/H/K, and N155H), while others retained susceptibility to RAL (T66I/A, E92G, T97A, and S147G). Dual combinations of primary IN mutations further reduced INSTI susceptibility, replication capacity, and viral fitness relative to either mutation alone. Susceptibility to DTG was retained by single primary IN mutations but reduced by dual mutation combinations with Q148R. Primary EVG RAMs also diminished IN enzymatic activities, concordant with their structural proximity to the active site. Greater reductions in viral fitness of dual mutation combinations may explain why some primary INSTI RAMs do not readily coexist on the same HIV-1 genome but rather establish independent pathways of resistance to EVG.

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