Low-Level K65R Mutation in HIV-1 Reverse Transcriptase of Treatment-Experienced Patients Exposed to Abacavir or Didanosine
| Autor: | Andrew Bae, Katyna Borroto-Esoda, Lijie Zhong, Nicolas A. Margot, Evguenia S. Svarovskaia, Derrick D. Goodman, Michael D. Miller, Joshua M. Waters |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Oncology
medicine.medical_specialty viruses Population Organophosphonates HIV Infections Viral quasispecies Polymerase Chain Reaction Double-Blind Method Abacavir Internal medicine Drug Resistance Viral Genotype medicine Humans Pharmacology (medical) Tenofovir education Didanosine Alleles education.field_of_study biology Reverse-transcriptase inhibitor Adenine biochemical phenomena metabolism and nutrition biology.organism_classification Virology Dideoxynucleosides HIV Reverse Transcriptase Reverse transcriptase Treatment Outcome Infectious Diseases Mutation Lentivirus HIV-1 Reverse Transcriptase Inhibitors medicine.drug |
| Zdroj: | JAIDS Journal of Acquired Immune Deficiency Syndromes. 46:174-180 |
| ISSN: | 1525-4135 |
| DOI: | 10.1097/qai.0b013e31814258c0 |
| Popis: | Background: Prior abacavir (ABC) or didanosine (ddI) therapy can result in the L74V/I or K65R mutation in HIV-1 reverse transcriptase. Preexisting K65R may have an impact on the treatment response to tenofovir disoproxil fumarate (TDF). Methods: An allele-specific polymerase chain reaction (AS-PCR) assay was developed to detect K65R with a lower limit of quantitation of 0.5%. Results: Among baseline plasma samples from 63 treatment-naive patients, no K65R was detected by AS-PCR. Among baseline samples from 154 treatment-experienced patients, 8 had K65R and 44 had L74V/I by population sequencing. Low-level K65R was detected in an additional 11 patients by AS-PCR, 3 of whom subsequently developed full K65R. Baseline K65R correlated with absence of thymidine analog mutations (TAMs; P = 0.003) and use of ABC or ddI (P = 0.004). Patients with full or low-level K65R at baseline or with L74V/I showed a diminished TDF response. Multivariate analyses confirmed that multiple TAMs, K65R, and L74V/I were independent predictors of diminished TDF response. Conclusions: Prior therapy with ABC or ddI can result in a population genotype that shows K65R or L74V/I but does not reveal low-level K65R present in some patients. Subsequent treatment intensification with TDF resulted in a poor virologic response and may result in expansion of the preexisting K65R mutant. |
| Databáze: | OpenAIRE |
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