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Means and method for monitoring antiretroviral therapy and guiding therapeutic decisions in treatment of HIV/AIDS

A technique of transcribing virus and reverse transcriptase, which is applied in the direction of retroRNA virus, antiviral agent, virus/bacteriophage, etc., and can solve the problem of not detecting the change of azide thymidine sensitivity

Inactive Publication Date: 2003-10-01
病毒科学公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

No change in sensitivity to zidovudine was detected in this study (Staszewski S, Massari FE, Kober A, et al. (1995) Jinfect Dis 171, 1159-1165)

Method used

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  • Means and method for monitoring antiretroviral therapy and guiding therapeutic decisions in treatment of HIV/AIDS
  • Means and method for monitoring antiretroviral therapy and guiding therapeutic decisions in treatment of HIV/AIDS
  • Means and method for monitoring antiretroviral therapy and guiding therapeutic decisions in treatment of HIV/AIDS

Examples

Experimental program
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Effect test

Embodiment 1

[0123] Phenotypic drug susceptibility and resistance testing using resistance test vectors

[0124] Phenotypic drug susceptibility and resistance testing was performed using the manner and methods described in PCT International Application No. PCT / US97 / 01609, filed January 29, 1997, which application is hereby incorporated by reference.

[0125] In these experiments, patient-derived fragments (PDS) corresponding to the HIV protease (PR) and reverse transcriptase coding regions, or viral RNA isolated from viral particles present in the sera of HIV-infected individuals by inversion A patient-derived fragment amplified by RT-PCR, or a mutant form of wild-type HIV-1 produced by directed mutagenesis of a parental clone of resistance test vector DNA. Isolation of viral RNA was performed using standard procedures (eg, RNAgents Total RNA Isolation System, Promega, Madison WI or RNAzol, Tel-Test, Friendswood, TX). The RT-PCR method is divided into two steps. Retroviral reverse t...

Embodiment 2

[0134] Correlation Phenotypic Sensitivity and Genotyping Phenotypic Sensitivity Analysis of Patient HIV Samples

[0135] The resistance test vector was constructed as described in Example 1. Resistance test vectors or clones derived from resistance test vector libraries are tested in phenotypic assays to accurately and quantitatively determine the level of susceptibility to a panel of antiretroviral drugs. The group of antiretroviral drugs may contain members of the classes commonly known as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PRIs). This panel of drugs can be extended to new drugs or new drug targets that are available. IC50s were determined for each resistance test vector pool for each test drug. The susceptibility patterns to all tested drugs were examined and compared to known susceptibility patterns. The drug's effect on viral replication (ie, luciferase ac...

Embodiment 3

[0139] In HIV, use of resistance test vectors and site-directed mutants to correlate genotypes and associated phenotypes with NNRTI drug sensitivity and resistance, and drug-dependent stimulation of replication

[0140] From: Preparation of M230L+Y181C resistance test vector and phenotypic analysis of patient ARG-014 HIV samples

[0141] Resistance test vectors were constructed as described in Example 1 from virus samples from individual patients sampled at three time points over a 16-week interval. The patient had been treated with two NRTIs (dideoxyadenosine and lamivudine) and one PRI, indinavir. At the time the first sample (designated 98-773) was obtained, the patient was started on a new antiviral regimen consisting of: NRTI (abacavir), NNRTI (nevirapine) and two PRI's s (nelfinavir and saquinavir) (PRIs). A second sample (98-1046) was obtained after 8 weeks and a third sample (98-887) was obtained after 16 weeks. Viral load measurements showed that ...

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Abstract

The present invention relates to antiviral drug susceptibility and resistance assays for identifying effective drug regimens for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), and to monitoring the clinical progression of HIV infection and Modes and methods of HIV infection response to antiretroviral therapy, in particular nucleoside reverse transcriptase inhibitor therapy using phenotypic sensitivity analysis and genotypic analysis.

Description

[0001] Throughout this application, the authors reference and date various publications. Full citations to these publications are listed alphabetically at the end of the specification, immediately preceding the claims. All patents, patent applications and publications cited herein, whether supra or infra, are hereby incorporated by reference in their entirety. The disclosures of these publications in their entireties are hereby incorporated by reference for the purpose of more fully describing the state of the art, known to those skilled in the art, as of the date of the invention described and claimed herein. technical field [0002] The present invention relates to antiretroviral drug susceptibility and resistance assays for use in identifying effective drug regimens for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). The present invention also relates to means and methods for monitoring the clinical progression o...

Claims

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Application Information

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IPC IPC(8): C12N15/09A61K45/00A61P31/18C07K14/16C12N15/867C12Q1/02C12Q1/68C12Q1/70
CPCA61P31/18C07K14/005C12N15/86C12N2740/16043C12N2740/16122C12Q1/703
Inventor 珍尼特·惠特科姆
Owner 病毒科学公司
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