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Tipranavir-Ritonavir Genotypic Resistance Score in Protease Inhibitor-Experienced Patients
- Source :
- Antimicrobial Agents and Chemotherapy. 52:3237-3243
- Publication Year :
- 2008
- Publisher :
- American Society for Microbiology, 2008.
-
Abstract
- To identify mutations associated with the virological response (VR) to a tipranavir-ritonavir (TPV/r)-based regimen, 143 patients previously treated with protease inhibitor (PI) were studied. VR was defined by a decrease of at least 1 log10in, or undetectable, human immunodeficiency virus (HIV) RNA at month 3. The effect of each mutation in the protease, considering all variants at a residue as a single variable, on the VR to TPV/r was investigated. Mutations at six residues were associated with a lower VR (E35D/G/K/N, M36I/L/V, Q58E, Q61D/E/G/H/N/R, H69I/K/N/Q/R/Y, and L89I/M/R/T/V), and one mutation was associated with a higher VR (F53L/W/Y). The genotypic score M36I/L/V − F53L/W/Y + Q58E + H69I/K/N/Q/R/Y + L89I/M/R/T/V was selected as providing a strong association with VR. For the seven patients with a genotypic score of −1 (viruses with only mutation at codon 53), the percentage of responders was 100% and the percentages were 79%, 56%, 33%, 21%, and 0% for those with scores of 0, 1, 2, 3, and 4, respectively. The percentage of patients showing a response to TPV/r was lower for patients infected with non-clade B viruses (n= 16, all non-B subtypes considered together) than for those infected with clade B viruses (n= 127) (25% and 59%, respectively;P= 0.015). Most mutations associated with VR to TPV/r had not previously been associated with PI resistance. This is consistent with phenotypic analysis showing that TPV has a unique resistance profile. Mutations at five positions (35, 36, 61, 69, and 89) were observed significantly more frequently in patients infected with a non-B subtype than in those infected with the B subtype, probably explaining the lower VR observed in these patients.
- Subjects :
- Male
Genotype
Anti-HIV Agents
Pyridines
medicine.medical_treatment
HIV Infections
Biology
medicine.disease_cause
Antiviral Agents
HIV Protease
Drug Resistance, Viral
medicine
Humans
HIV Protease Inhibitor
Pharmacology (medical)
Protease inhibitor (pharmacology)
Pharmacology
Sulfonamides
Mutation
Ritonavir
Protease
HIV Protease Inhibitors
Virology
Infectious Diseases
Pyrones
Enzyme inhibitor
HIV-1
biology.protein
Reverse Transcriptase Inhibitors
Drug Therapy, Combination
Female
Tipranavir
medicine.drug
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....5f6bcccb5cc3c2c827175c39d55e5758