Related Experiment Video
Updated: Jun 8, 2026
05:46
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Evolution patterns of raltegravir-resistant mutations after integrase inhibitor interruption.
F Canducci1, B Barda, E Ceresola
1Laboratorio di Microbiologia e Virologia, Università Vita-Salute San Raffaele, Milano, Italy. Canducci.filippo@hsr.it
Summary
Raltegravir resistance mutations in human immunodeficiency virus type 1 (HIV-1) reverted to wild-type in most patients after stopping the drug. However, resistance mutations persisted in some patients, indicating complex viral dynamics.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Raltegravir is an integrase inhibitor used to treat HIV-1 infection.
- Virological failure can occur due to the selection of drug-resistant HIV-1 variants.
- Understanding the evolution of resistance mutations after drug interruption is crucial for treatment strategies.
Purpose of the Study:
- To investigate the reversion of HIV-1 integrase inhibitor resistance mutations after raltegravir treatment interruption.
- To identify factors influencing the persistence or reversion of resistance mutations in HIV-1 variants.
Main Methods:
- Prospective monitoring of 13 HIV-1 infected patients experiencing virological failure on raltegravir.
- Analysis of clinical, virological, and immunological parameters, including HIV-1 viraemia and CD4(+) T-cell counts.
- Sequence analysis of HIV-1 integrase to track resistance mutations over time after drug withdrawal.
Main Results:
- Reversion to wild-type HIV-1 integrase sequence occurred in 8 out of 13 patients within 4-36 weeks of raltegravir withdrawal.
- In 5 patients, complete reversion was not observed, with resistance mutations persisting.
- Rapid reversion was observed in some cases, even under different therapy regimens or 3TC monotherapy.
Conclusions:
- HIV-1 variants with raltegravir resistance mutations can become undetectable after drug interruption in a majority of patients.
- The persistence of resistance mutations in some individuals suggests that other factors influence this evolutionary process.
- These findings have implications for managing HIV-1 treatment and understanding drug resistance dynamics.
More Related Videos
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...
01:22Antiviral 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),...
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’...
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...