ArticleJournal of virology2003
A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation.
Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 89 citations in OpenAlex.
- Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia.PloS one · 2013Trial
- Progression of Antiviral Agents Targeting Viral Polymerases.Molecules (Basel, Switzerland) · 2022Review
- Discovery and Development of Anti-HIV Therapeutic Agents: Progress Towards Improved HIV Medication.Current topics in medicinal chemistry · 2019Review
- An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs.The Journal of antimicrobial chemotherapy · 2017Article
- Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors.Nucleic acids research · 2016Article
- Efficacy of topical tenofovir against transmission of a tenofovir-resistant SHIV in macaques.Retrovirology · 2015Article
- Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine.The Journal of infectious diseases · 2013Article
- Comparative analysis of drug resistance among B and the most prevalent non-B HIV type 1 subtypes (C, F, and CRF02_AG) in Italy.AIDS research and human retroviruses · 2012Article
- HIV-1 antiretroviral drug therapy.Cold Spring Harbor perspectives in medicine · 2012Review
- Low-abundance HIV species and their impact on mutational profiles in patients with virological failure on once-daily abacavir/lamivudine/zidovudine and tenofovir.The Journal of antimicrobial chemotherapy · 2010Article
- Article
- Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.Journal of acquired immune deficiency syndromes (1999) · 2009Article
- The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy.AIDS (London, England) · 2009Article
- Apricitabine does not select additional drug resistance mutations in tissue culture in human immunodeficiency virus type 1 variants containing K65R, M184V, or M184V plus thymidine analogue mutations.Antimicrobial agents and chemotherapy · 2009Article
- Review
- The fitness cost of mutations associated with human immunodeficiency virus type 1 drug resistance is modulated by mutational interactions.Journal of virology · 2007Article
- High prevalence of the K65R mutation in human immunodeficiency virus type 1 subtype C isolates from infected patients in Botswana treated with didanosine-based regimens.Antimicrobial agents and chemotherapy · 2006Article
- MultiCode-RTx real-time PCR system for detection of subpopulations of K65R human immunodeficiency virus type 1 reverse transcriptase mutant viruses in clinical samples.Journal of clinical microbiology · 2006Article
- The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations.Journal of virology · 2006Article
- Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation.Journal of clinical microbiology · 2005Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stavudine (d4T) and zidovudine (AZT) are thymidine analogs widely used in the treatment of human immunodeficiency virus type 1 (HIV-1)-infected persons. Resistance to d4T is not fully understood, although the selection of AZT resistance mutations in patients treated with d4T suggests that both drugs have similar pathways of resistance. Through the analysis of genotypic changes in nine recombinant viruses cultured with d4T, we identified a new pathway for d4T resistance mediated by K65R, a mutation not selected by AZT. Passaged viruses were derived from treatment-naïve persons or HIV-1(HXB2) and had wild-type reverse transcriptase (RT) or T215C/D mutations. K65R was selected in seven viruses and was associated with a high level of enzymatic resistance to d4T-triphosphate (median, 16-fold; range, 5- to 48-fold). The role of K65R in d4T resistance was confirmed in site-directed mutants generated in three different RT backgrounds. Phenotypic assays based on recombinant single-cycle replication or a whole-virus multiple replication cycle were unable to detect d4T resistance in d4T-selected mutants with K65R but detected cross-resistance to other nucleoside RT inhibitors. Four of the six viruses that had 215C/D mutations at baseline acquired the 215Y mutation alone or in association with K65R. Mutants having K65R and T215Y replicated less efficiently than viruses that had T215Y only, suggesting that selection of T215Y in patients treated with d4T may be favored. Our results demonstrate that K65R plays a role in d4T resistance and indicate that resistance pathways for d4T and AZT may not be identical. Biochemical analysis and improved replication assays are both required for a full phenotypic characterization of resistance to d4T. These findings highlight the complexity of the genetic pathways of d4T resistance and its phenotypic expression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.