Related Experiment Video
Updated: Jul 26, 2026
19:57
An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings
Published on: March 30, 2014
HIV-1 reverse transcriptase mutations found in a drug-experienced patient confer reduced susceptibility to multiple
J E Fitzgibbon1, B DiCola, E Arnold
1Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, USA. fitzg@umdnj.edu
Antiviral Therapy
|March 7, 2002
Summary
Stavudine resistance mutations are rare in patients. However, a heavily treated patient developed novel mutations conferring multi-drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs).
Area of Science:
- Virology
- Antimicrobial Resistance
Background:
- Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV-1.
- Understanding drug resistance mutations is crucial for effective HIV-1 treatment.
- Previous studies indicate stavudine resistance mutations are uncommon.
Purpose of the Study:
- To investigate HIV-1 reverse transcriptase (RT) genotypes in patients treated with stavudine.
- To identify any novel or known mutations associated with stavudine resistance.
- To assess the impact of identified mutations on NRTI susceptibility.
Main Methods:
- HIV-1 RT genotyping was performed on 13 stavudine-treated patients.
- A chimeric virus was constructed using RT sequences from a heavily treated patient.
- The chimeric virus was tested for susceptibility to multiple nucleoside RT inhibitors (NRTIs).
Main Results:
- No previously reported stavudine resistance mutations were found in most patients.
- One heavily treated patient harbored a novel V75M mutation in the RT.
- A chimeric virus with V75M and other resistance mutations showed reduced susceptibility to multiple NRTIs, with V75M contributing to didanosine and lamivudine resistance.
Conclusions:
- Stavudine resistance mutations are rare, aligning with previous findings.
- A novel set of mutations, including V75M, can confer multi-drug resistance to NRTIs in heavily treated patients.
- Increased vigilance for multi-drug resistance is essential in patients with extensive NRTI treatment history.
Related Concept Videos
01:10Retrovirus Life Cycles
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
00:36Viral Mutations
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...
01:26Size and Structure of Viral Genomes
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
01:29Viruses with RNA Genomes
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
01:22Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
01:19Inhibitors of Virion Maturation and Assembly
As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...