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Related Concept Videos

Retrovirus Life Cycles01:10

Retrovirus 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...

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Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with

Hiroyu Hatano1, Matthew C Strain, Rebecca Scherzer

  • 1Department of Medicine.

The Journal of Infectious Diseases
|August 27, 2013
PubMed
Summary

Raltegravir intensification increased viral markers (2-LTR circles) in HIV patients on long-term ART, suggesting persistent low-level replication. This treatment also reduced D-dimer levels, a marker of morbidity and mortality.

Keywords:
2-LTR circlesD-dimerHIVongoing viral replicationraltegravir intensification

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Area of Science:

  • Virology
  • Immunology
  • Pharmacology

Background:

  • The extent of human immunodeficiency virus (HIV) replication during antiretroviral therapy (ART) remains a subject of debate.
  • Persistent low-level HIV replication may impact long-term patient outcomes.

Purpose of the Study:

  • To investigate whether raltegravir intensification can reduce low-level viral replication in individuals with suppressed HIV.
  • To assess the impact of raltegravir intensification on 2-long terminal repeat (2-LTR) circles as a marker of viral replication.

Main Methods:

  • A randomized, double-blind, placebo-controlled study involving 31 subjects with suppressed HIV RNA levels (<40 copies/mL) on ART for at least one year.
  • Participants received either raltegravir (400 mg twice daily) or a placebo for 24 weeks, with 2-LTR circle levels measured at baseline and weeks 1, 2, and 8 using droplet digital polymerase chain reaction.

Main Results:

  • Raltegravir intensification led to a significant increase in 2-LTR circle levels compared to placebo, with week 1 and week 2 ratios 8.8-fold and 5.7-fold higher, respectively.
  • The study observed a statistically significant decrease in D-dimer levels in the raltegravir group compared to the placebo group (P = .045).

Conclusions:

  • Raltegravir intensification rapidly increased 2-LTR circles in a subset of patients, indicating that low-level HIV replication persists even after long-term ART.
  • HIV treatment intensification with raltegravir also demonstrated a beneficial effect by reducing D-dimer levels, a biomarker associated with increased morbidity and mortality in HIV-infected individuals.