Related Experiment Video
Updated: Jun 23, 2026
10:29
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Clinical implications of mutations at reverse transcriptase codon 135 on response to NNRTI-based therapy
Harout K Tossonian1, Jesse D Raffa, Jason Grebely
1Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
The Open Virology Journal
|May 15, 2009
Summary
Mutations at reverse transcriptase codon 135 do not impact treatment response rates in patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy. However, these mutations influence the development pattern of NNRTI resistance mutations.
Area of Science:
- Virology
- Infectious Diseases
- Pharmacogenomics
Background:
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a cornerstone of antiretroviral therapy for HIV.
- Understanding mutations in reverse transcriptase, specifically at codon 135, is crucial for optimizing treatment outcomes.
- The emergence of drug resistance necessitates continuous evaluation of treatment strategies.
Purpose of the Study:
- To assess the effect of baseline mutations at reverse transcriptase codon 135 on treatment outcomes in patients receiving NNRTI-based antiretroviral therapy.
- To investigate how these mutations influence the development of NNRTI resistance patterns.
Main Methods:
- A cohort of 68 patients receiving NNRTI-based antiretroviral therapy was analyzed.
- Patients were categorized based on the presence or absence of baseline mutations at reverse transcriptase codon 135.
- Treatment outcomes, including CD4 count changes, virologic suppression rates, and the emergence of NNRTI resistance mutations, were evaluated.
Main Results:
- No significant differences were observed in median CD4 count increases or virologic suppression rates between patients with and without codon 135 mutations.
- NNRTI resistance was detected in a high proportion of patients in both groups.
- Patients with baseline codon 135 mutations were more likely to develop single NNRTI resistance mutations but less likely to develop multiple mutations upon virologic breakthrough.
Conclusions:
- Mutations at reverse transcriptase codon 135 do not appear to affect the initial response rates to NNRTI-based therapy.
- These mutations significantly alter the pattern of NNRTI resistance mutation development, favoring single over multiple mutations.
- Findings have implications for the selection of newer NNRTIs, such as etravirine, in salvage therapy regimens.
Related Concept Videos
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...
01:22Antiviral 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),...
01:10Retrovirus 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...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
02:33Retroviruses
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...