Phenotypic Changes in Drug Susceptibility Associated with Failure of Human Immunodeficiency Virus Type 1 (HIV-1) Triple Combination Therapy

The emergence of drug-resistant human immunodeficiency virus type 1 is a frequent cause of failure of combination therapies comprising reverse transcriptase and protease inhibitors. Rational design of salvage therapies requires new methods to assess drug susceptibility. A novel phenotypic drug susce...

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Bibliographic Details
Published in:The Journal of infectious diseases 1999-09, Vol.180 (3), p.865-870
Main Authors: Parkin, Neil T., Lie, Yolanda S., Hellmann, Nicholas, Markowitz, Martin, Bonhoeffer, Sebastian, Ho, David D., Petropoulos, Christos J.
Format: Article
Language:English
Subjects:
Acquired Immunodeficiency Syndrome - blood
Acquired Immunodeficiency Syndrome - drug therapy
AIDS
AIDS/HIV
Anti-HIV Agents - pharmacology
Anti-HIV Agents - therapeutic use
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiretrovirals
Antiviral agents
Antivirals
Biological and medical sciences
Cell Line
Concise Communications
Drug resistance
Drug Resistance, Microbial
Drug Therapy, Combination
Genetic mutation
Genotype
HIV 1
HIV-1 - drug effects
HIV-1 - genetics
HIV-1 - isolation & purification
Human immunodeficiency virus 1
Human viral diseases
Humans
Infections
Infectious diseases
Inhibitory concentration 50
Lamivudine - therapeutic use
Medical sciences
Microbial Sensitivity Tests
nelfinavir
Nelfinavir - therapeutic use
Pharmacology. Drug treatments
Phenotype
Salvage Therapy
Time Factors
Transfection
Treatment Failure
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
Viruses
Zidovudine - therapeutic use
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Description
Summary:The emergence of drug-resistant human immunodeficiency virus type 1 is a frequent cause of failure of combination therapies comprising reverse transcriptase and protease inhibitors. Rational design of salvage therapies requires new methods to assess drug susceptibility. A novel phenotypic drug susceptibility assay was developed and used to measure the drug susceptibilities of viruses obtained from 2 patients treated with zidovudine, lamivudine, and nelfinavir. Results showed that phenotypic drug resistance may be detectable before virus load rebound, treatment failure does not always imply viral resistance to all drugs in a treatment regimen, and persons with similar antiviral treatment histories and clinical courses may have different phenotypic drug resistance profiles at the time that treatment fails.
ISSN:0022-1899
1537-6613
DOI:10.1086/314928