In:
Antiviral Therapy, SAGE Publications, Vol. 17, No. 2 ( 2012-02), p. 355-364
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. 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. ClinicalTrials.gov identifier: NCT00554398.
Type of Medium:
Online Resource
ISSN:
1359-6535
,
2040-2058
Language:
English
Publisher:
SAGE Publications
Publication Date:
2012
detail.hit.zdb_id:
2118396-X
SSG:
15,3
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