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

Research paper by Josep M JM Llibre, Maria J MJ Buzón, Marta M Massanella, Anna A Esteve, Viktor V Dahl, Maria C MC Puertas, Pere P Domingo, Josep M JM Gatell, Maria M Larrouse, Mar M Gutierrez, Sarah S Palmer, Mario M Stevenson, Julià J Blanco, Javier J Martinez-Picado, Bonaventura B Clotet

Indexed on: 01 Feb '12Published on: 01 Feb '12Published in: Antiviral therapy



Abstract

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.This was a prospective, open-label, randomized study comprising 69 individuals on suppressive HAART randomly assigned 2:1 to add raltegravir during 48 weeks.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.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. ClinicalTrials.gov identifier: NCT00554398.

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