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Human Immunodeficiency Virus Type 1 Protease Genotypes and In Vitro Protease Inhibitor Susceptibilities of Isolates from Individuals Who Were Switched to Other Protease Inhibitors after Long-Term Saquinavir Treatment
- Source :
- Journal of Virology. 72:5303-5306
- Publication Year :
- 1998
- Publisher :
- American Society for Microbiology, 1998.
-
Abstract
- An understanding of the mechanisms of virologic cross-resistance between human immunodeficiency virus type 1 protease inhibitors is important for the establishment of effective treatment strategies for patients who no longer respond to their initial protease inhibitor. Protease gene sequencing results from patients treated with saquinavir showed significant increases in the frequency of the G48V protease mutation in patients receiving higher doses of the drug. In addition, all six patients who developed the G48V mutation during saquinavir therapy developed the V82A mutation either on continued saquinavir or after a switch to nelfinavir or indinavir. In vitro susceptibility assays showed that all 13 isolates with reduced susceptibilities to two or more protease inhibitors had either the G48V or L90M mutation, along with an average of six other protease mutations. Reduced susceptibility to nelfinavir was found in 14 isolates, but only 1 possessed the D30N mutation. These results suggest that mutations selected in vivo by initial saquinavir therapy may provide more cross-resistance to the other protease inhibitors than has been previously reported.
- Subjects :
- Time Factors
viruses
medicine.medical_treatment
Immunology
HIV Infections
Genome, Viral
Biology
medicine.disease_cause
Microbiology
HIV Protease
Indinavir
Virology
Genotype
medicine
Humans
HIV Protease Inhibitor
Protease inhibitor (pharmacology)
Mutation
Protease
HIV Protease Inhibitors
biochemical phenomena, metabolism, and nutrition
Virus-Cell Interactions
Nelfinavir
Insect Science
HIV-1
Saquinavir
medicine.drug
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 72
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi.dedup.....9428dc1a3df54cfbe60ee190ce9c74d2