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J Antimicrob Chemother. 2013 Oct;68(10):2358-62. doi: 10.1093/jac/dkt183. Epub 2013 May 14.

Early but limited effects of raltegravir intensification on CD4 T cell reconstitution in HIV-infected patients with an immunodiscordant response to antiretroviral therapy.

Author information

1
Lluita contra la SIDA foundation, Institut de Recerca en Ciències de la Salut Germans Trias i Pujol (IGTP), Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.

Abstract

BACKGROUND:

Immune hyperactivation in immunodiscordant patients can induce residual HIV replication and limit CD4 T cell recovery. We assessed the impact of raltegravir intensification on CD4 T cell recovery and viral persistence.

METHODS:

We performed a randomized, controlled, pilot trial. Patients with CD4 T cell counts <350 cells/mm(3) despite suppressive antiretroviral therapy were randomized (2 : 1) to intensify with raltegravir (intensified arm, n = 30) or to continue with the same regimen (control arm, n = 14) for 48 weeks. Then, the control individuals intensified their treatment for 24 weeks (delayed-intensification arm). We analysed changes in CD4 T cell counts, total and episomal HIV DNA in peripheral blood mononuclear cells and predictive factors for response.

RESULTS:

Raltegravir intensification induced a rapid increase in CD4 T cell counts (week 12) (P = 0.007), although this was not sustained over time. Control patients maintained constant but slow increases in CD4 T cell counts (present in the pre-study period), reaching CD4 T cell counts similar to those of patients in the intensification arm at week 48. This effect was confirmed by the analysis of the delayed-intensification arm. Proviral DNA levels remained stable in both arms over time; episomal DNA forms and ultrasensitive plasma viral load were barely detected during the study. Increases in CD4 T cell counts were associated with low baseline CD95 expression in CD4 and CD8 T cells (P = 0.020).

CONCLUSIONS:

Raltegravir intensification modestly impacts viral dynamics and induces a rapid but limited gain in CD4 T cell counts in immunodiscordant patients. Residual viral replication does not seem to be the main cause of unsatisfactory CD4 T cell recovery in these patients.

KEYWORDS:

discordant patients; immune recovery; integrase inhibitor; viral suppression

PMID:
23677919
PMCID:
PMC4439517
DOI:
10.1093/jac/dkt183
[Indexed for MEDLINE]
Free PMC Article
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