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Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study
- Source :
- Journal of Antimicrobial Chemotherapy
- Publisher :
- OXFORD UNIV PRESS
-
Abstract
- Author(s): Dolling, David I; Dunn, David T; Sutherland, Katherine A; Pillay, Deenan; Mbisa, Jean L; Parry, Chris M; Post, Frank A; Sabin, Caroline A; Cane, Patricia A; UK HIV Drug Resistance Database (UKHDRD); UK Collaborative HIV Cohort Study (UK CHIC) | Abstract: ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P l 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P l 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.
- Subjects :
- Male
Mutation rate
Pyridines
Human immunodeficiency virus (HIV)
HIV Infections
medicine.disease_cause
THERAPY
Cohort Studies
0302 clinical medicine
HIV Protease
Mutation Rate
1108 Medical Microbiology
Genotype
Pharmacology (medical)
030212 general & internal medicine
Pharmacology & Pharmacy
Treatment Failure
drug resistance mutations
Original Research
0303 health sciences
virological failure
UK Collaborative HIV Cohort Study (UK CHIC)
Proteolytic enzymes
virus diseases
Middle Aged
3. Good health
Infectious Diseases
Female
1115 Pharmacology and Pharmaceutical Sciences
Life Sciences & Biomedicine
Oligopeptides
medicine.drug
Cohort study
0605 Microbiology
Microbiology (medical)
Adult
medicine.medical_specialty
Anti-HIV Agents
Atazanavir Sulfate
protease inhibitors
Mutation, Missense
RITONAVIR
Biology
Microbiology
Medication Adherence
03 medical and health sciences
Internal medicine
SCORE
Drug Resistance, Viral
medicine
Humans
030304 developmental biology
Pharmacology
Science & Technology
HIV
Virology
naive patients
United States
Atazanavir
Regimen
HIV-1
Ritonavir
UK HIV Drug Resistance Database (UKHDRD)
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of Antimicrobial Chemotherapy
- Accession number :
- edsair.doi.dedup.....a76fc2c1844834a6f30ff55650812c1a