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

Abstract

Background:Immune hyperactivation in immunodiscordant patients can induce residual HIV replication and limit CD4Tcell recovery. We assessed theimpact of raltegravir intensification onCD4 T cell recoveryandviral persistence.Methods: We performed a randomized, controlled, pilot trial. Patients with CD4 T cell counts <350 cells/mm3 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 Tcell counts (week 12) (P=0.007), although this was not sustained over time. Control patients maintained constant but slowincreases in CD4 Tcell counts (present in the pre-study period), reaching CD4 Tcell counts similar to those of patients in the intensificationarmatweek 48. This effectwas 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. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.