scholarly journals Comparative Analysis of Two Commercial Phenotypic Assays for Drug Susceptibility Testing of Human Immunodeficiency Virus Type 1

2002 ◽  
Vol 40 (1) ◽  
pp. 31-35 ◽  
Author(s):  
S. H. Qari ◽  
R. Respess ◽  
H. Weinstock ◽  
E. M. Beltrami ◽  
K. Hertogs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Comparative Analysis ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Immunodeficiency Virus

scholarly journals Rapid and Simple Phenotypic Assay for Drug Susceptibility of Human Immunodeficiency Virus Type 1 Using CCR5-Expressing HeLa/CD4+ Cell Clone 1-10 (MAGIC-5)

2001 ◽  
Vol 45 (2) ◽  
pp. 495-501 ◽  
Author(s):  
Atsuko Hachiya ◽  
Saori Aizawa-Matsuoka ◽  
Mari Tanaka ◽  
Yukiko Takahashi ◽  
Setsuko Ida ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cell Clone ◽  
Drug Susceptibility ◽  
Phenotypic Resistance ◽  
Phenotypic Assay ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We describe a rapid and simple novel phenotypic assay for drug susceptibility of human immunodeficiency virus type-1 (HIV-1) using a CCR5-expressing HeLa/CD4+ cell clone 1-10 (MAGIC-5). MAGIC-5 cells produced large amounts of HIV-1 in culture supernatants, which enabled us to perform the phenotypic resistance assay. Determination of HIV-1 susceptibility to various protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors was completed within 15 days in T-cell-tropic (X4) and macrophage-tropic (R5) viruses using fresh plasma samples containing at least 104copies/ml. The nucleotide sequence of the envelope V3 region of HIV-1 in plasma was almost identical to that of the virus isolated by MAGIC-5 cells, suggesting a lack of selection bias in our assay. The assay variability was confined to within five-fold in all drugs examined. Accordingly, we used a 10-fold increase in the 50% inhibitory concentration as the cutoff value for viral resistance in the present assay. HIV-1 resistant to lamivudine, which was not detected by conventional genotypic assays, was isolated. In HIV-1 with PI-associated primary amino acid substitutions, our assay showed that drug resistance profiles correlated well with previously reported genotypic-assay data. Furthermore, our assay provided comprehensive results regarding PI resistance in the presence of multiple mutations. The novel assay successfully quantified the level of resistance of clinical HIV-1 isolates to a battery of anti-HIV drugs, indicating its clinical usefulness, particularly in patients who failed to respond to antiretroviral chemotherapy.

scholarly journals Variants Other than Aspartic Acid at Codon 69 of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Gene Affect Susceptibility to Nucleoside Analogs

2001 ◽  
Vol 45 (8) ◽  
pp. 2276-2279 ◽  
Author(s):  
Mark A. Winters ◽  
Thomas C. Merigan
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Gene Mutations ◽  
Nucleoside Analogs ◽  
Drug Susceptibility ◽  
Immunodeficiency Virus ◽  
Rt Inhibitors

ABSTRACT The T69D mutation in the human immunodeficiency virus type 1 reverse transcriptase (RT) gene has been associated with reduced susceptibility to dideoxycytosine (ddC); however, several other mutations at codon 69 have been observed in antiretroviral drug-treated patients. The Stanford HIV RT and Protease Sequence Database was interrogated and showed that 23% of patients treated with nucleoside RT inhibitors (NRTI) had mutations at codon 69. These variants included T69N, -S, -A, -G, -E, -I, and -K mutations that were present in patients treated with NRTI but not in drug-naive patients. Treatment history information showed that a substantial percentage of these codon 69 changes occurred in patients administered non-ddC-containing regimens. Different and specific patterns of other RT gene mutations were associated with the various codon 69 mutations. Drug susceptibility assays showed that viral constructs containing codon 69 variants could have reduced susceptibility to ddC and other RT inhibitors. These results suggest that the T69D mutation is not the only codon 69 variant associated with drug resistance and that ddC is not the only drug affected.

scholarly journals The Impact of Individual Human Immunodeficiency Virus Type 1 Protease Mutations on Drug Susceptibility Is Highly Influenced by Complex Interactions with the Background Protease Sequence

2009 ◽  
Vol 83 (18) ◽  
pp. 9512-9520 ◽  
Author(s):  
H. Van Marck ◽  
I. Dierynck ◽  
G. Kraus ◽  
S. Hallenberger ◽  
T. Pattery ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Drug Susceptibility ◽  
Vast Number ◽  
Complex Interactions ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

ABSTRACT The requirement for multiple mutations for protease inhibitor (PI) resistance necessitates a better understanding of the molecular basis of resistance development. The novel bioinformatics resistance determination approach presented here elaborates on genetic profiles observed in clinical human immunodeficiency virus type 1 (HIV-1) isolates. Synthetic protease sequences were cloned in a wild-type HIV-1 background to generate a large number of close variants, covering 69 mutation clusters between multi-PI-resistant viruses and their corresponding genetically closely related, but PI-susceptible, counterparts. The vast number of mutants generated facilitates a profound and broad analysis of the influence of the background on the effect of individual PI resistance-associated mutations (PI-RAMs) on PI susceptibility. Within a set of viruses, all PI-RAMs that differed between susceptible and resistant viruses were varied while maintaining the background sequence from the resistant virus. The PI darunavir was used to evaluate PI susceptibility. Single sets allowed delineation of the impact of individual mutations on PI susceptibility, as well as the influence of PI-RAMs on one another. Comparing across sets, it could be inferred how the background influenced the interaction between two mutations, in some cases even changing antagonistic relationships into synergistic ones or vice versa. The approach elaborates on patient data and demonstrates how the specific mutational background greatly influences the impact of individual mutations on PI susceptibility in clinical patterns.

scholarly journals The role of lysine residue at amino acid position 165 of human immunodeficiency virus type 1 CRF01_AE Gag in reducing viral drug susceptibility to protease inhibitors

Virology ◽  
2010 ◽  
Vol 405 (1) ◽  
pp. 129-138 ◽  
Author(s):  
Masanori Kameoka ◽  
Panasda Isarangkura-na-ayuthaya ◽  
Yoko Kameoka ◽  
Sompong Sapsutthipas ◽  
Bongkot Soonthornsata ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Protease Inhibitors ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Amino Acid Position ◽  
Drug Susceptibility ◽  
Immunodeficiency Virus
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