Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: A randomized 48-week study

Josep M. Llibre, Maria J. Buzón, Marta Massanella, Anna Esteve, Viktor Dahl, Maria C. Puertas, Pere Domingo, Josep M. Gatell, Maria Larrouse, Gutierrez Mar, Sarah Palmer, Mario Stevenson, Julià Blanco, Javier Martinez-Picado, Bonaventura Clotet

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Background: Residual viraemia is a major obstacle to HIV-1 eradication in subjects receiving HAART. The intensification with raltegravir could impact latent reservoirs and might lead to a reduction of plasma HIV-1 viraemia (viral load [VL]), complementary DNA intermediates and immune activation. Methods: This was a prospective, open-label, randomized study comprising 69 individuals on suppressive HAART randomly assigned 2:1 to add raltegravir during 48 weeks. Results: Total and integrated HIV-1 DNA, and ultrasensitive VL remained stable despite intensification. There was a significant increase in episomal HIV DNA at weeks 2-4 in the raltegravir group returning to baseline levels at week 48. Median CD4 + T-cell counts increased 124 and 80 cells/μl in the intensified and control groups after 48 weeks (P=0.005 and P=0.027, respectively), without significant differences between groups. No major changes were observed in activation of CD4 + T-cells. Conversely, raltegravir intensification significantly reduced activation of CD8 + T-cells at week 48 (HLA-DR +CD38 +, P=0.005), especially in the memory compartment (CD38 + of CD8 +CD45RO +, P<0.0001). Linear mix models also depicted a larger decrease in CD8 + T-cell activation in the intensification group (P=0.036 and P=0.010, respectively). Raltegravir intensification was not associated to any particular adverse event. Conclusions: Intensification of HAART with raltegravir during 48 weeks was safe and associated with a significant decrease in CD8 + T-cell activation, and a transient increase of episomal HIV-1 DNA. However, raltegravir did not significantly contribute to changes in CD4 + T-cell counts, ultrasensitive VL, and total and integrated HIV-1 DNA. These findings suggest that raltegravir impacts residual HIV-1 replication and support new strategies to impair HIV-1 persistence.

Original languageEnglish (US)
Pages (from-to)355-364
Number of pages10
JournalAntiviral Therapy
Volume17
Issue number2
DOIs
StatePublished - 2012

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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