Details
- Autor(en) / Beteiligte
- Titel
- Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia
- Ist Teil von
- PloS one, 2013-08, Vol.8 (8), p.e73744
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- Multi-nucleos(t)ide resistance (MNR) mutations including Q151M, K65R mutations, and insertion at codon 69 of HIV-1 reverse transcriptase coding region may confer resistance to all molecules of nucleos(t)ide reverse transcriptase inhibitors (NRTI). The presence of these mutations is an emerging problem compromising non-nucleoside reverse transcriptase inhibitors and protease inhibitors-based therapies. Furthermore, factors associated with selection of these mutations are still not well defined. The current study aimed to evaluate the frequency and to characterize factors associated with the occurrence of multi-nucleos(t)ide resistance mutations among HIV-1 infected patients failing recommended first-line antiretroviral regimens in Cambodia. This is a retrospective analysis of HIV-1 drug resistance genotyping of 520 HIV-1 infected patients in virological failure (viral load > 250 copies/mL) while on first-line antiretroviral therapy in Cambodia with at least one reverse transcriptase inhibitor resistance associated mutation. Among these 520 patients, a total of 66 subjects (66/520, 12.7%) presented ≥ 1 MNR mutation, including Q151M, K65R, and Insert69 for 59 (11.3%), 29 (5.6%), and 2 (0.4%) patients, respectively. In multivariate analysis, both Q151M (p = 0.039) and K65R (p = 0.029) mutations were independently associated with current stavudine- compared to zidovudine-use. Such selection of mutations by stavudine drastically limits the choice of antiretroviral molecules available for second-line therapy in resource-limited settings. This finding supports the World Health Organization's recommendation for stavudine phase-out.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0073744Titel-ID: cdi_plos_journals_1428550108
- Format
- –
- Schlagworte
- Acquired immune deficiency syndrome, Acquired Immunodeficiency Syndrome, Acquired Immunodeficiency Syndrome - drug therapy, Acquired Immunodeficiency Syndrome - epidemiology, Acquired Immunodeficiency Syndrome - genetics, Adolescent, Adult, AIDS, Amino Acid Substitution, Anti-HIV Agents, Anti-HIV Agents - administration & dosage, Antiretroviral agents, Antiretroviral drugs, Antiretroviral therapy, Base Sequence, Cambodia, Cambodia - epidemiology, Care and treatment, Child, Child, Preschool, Codon, DNA polymerases, Drug resistance, Drug Resistance, Multiple, Viral, Drug Resistance, Multiple, Viral - genetics, Ethics, Female, Follow-Up Studies, Genetic aspects, Genotyping, Highly active antiretroviral therapy, HIV, HIV (Viruses), HIV Reverse Transcriptase, HIV Reverse Transcriptase - antagonists & inhibitors, HIV Reverse Transcriptase - genetics, HIV-1, HIV-1 - enzymology, HIV-1 - genetics, Human health and pathology, Human immunodeficiency virus, Humans, Infectious diseases, Insertion, Life Sciences, Male, Molecular Sequence Data, Multivariate analysis, Mutation, Mutation, Missense, Non-nucleoside reverse transcriptase inhibitors, Nucleoside reverse transcriptase inhibitors, Patients, Pharmaceutical sciences, Pharmacology, Protease inhibitors, Proteases, Proteinase inhibitors, Retrospective Studies, Reverse transcriptase inhibitors, RNA-directed DNA polymerase, Santé publique et épidémiologie, Stavudine, Stavudine - administration & dosage, Therapy, Zidovudine, Zidovudine - administration & dosage