CONTENIDO

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

14/05/2013

doi: 10.1093/jac/dkt183

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.

 

Read abstract online in Journal of Antimicrobial Chemotherapy

Eugènia Negredo1, Marta Massanella2, Maria C. Puertas2, Maria J. Buzón2, Jordi Puig1, Núria Pérez-Alvárez1,3, Josué Pérez-Santiago4, Anna Bonjoch1, José Moltó1, Antoni Jou1, Patricia Echeverría1, Josep M. Llibre1, Javier Martínez-Picado2,5, Bonaventura Clotet1,2 and Julià Blanco2

 

1Lluita 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 2IrsiCaixa-HIVACAT, 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 3Statistics and Operation Research Department, Technical University of Catalonia, Barcelona, Spain 4University of California San Diego, San Diego, California, USA 5Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

Grupos de IrsiCaixa vinculados: Genómica MicrobianaHIVACATRetrovirología y Estudios Clínicos (GREC)Virología e Inmunología Celular (VIC)