• Marta Massanella, Eugènia Negredo, Jordi Puig, Maria C Puertas, Maria J Buzón, Núria Pérez-Álvarez, Jorge Carrillo, Bonaventura Clotet, Javier Martínez-Picado, and Julià Blanco.
• AIDS Research Institute, IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Catalonia, Spain.
• AIDS. 2012 Nov 28; 26 (18): 2285-93.

BackgroundImmunodiscordant HIV-infected patients show viral suppression during antiretroviral therapy but fail to recover CD4 T cells. Immunodiscordance is characterized by partial CD4 T-cell immunodeficiency and increased inflammation, activation and immunosenescence in both CD4 and CD8 T cells.MethodsA randomized, controlled, 48-week intensification study to assess the effect of raltegravir on immunological parameters in immunodiscordant patients (CD4 cell counts <350 cells/μl; viral load <50 copies/ml for >2 years). Patients were randomized (2 : 1) to intensify therapy with raltegravir (intensified arm, n = 30) or continue with the same therapy (control arm, n = 14).ResultsBoth groups showed similar immunological baseline characteristics. CD4 T-cell counts increased faster in the intensified arm (P = 0.01, week 12). However, no differences between groups were observed at week 48. Additionally, no changes in thymic output (CD45RA(+)CD31(+) cells), activation (HLA-DR(+)CD95(+) cells) or ex-vivo cell death were observed in CD4 T cells at any time point intergroups or intragroups. Conversely, intensified arm showed significant decreases in the expression of the CD8 T-cell activation marker CD38 at weeks 24-48, which were more evident in memory cells. Despite this, the levels of HLA-DR expression in CD8 T cells and plasma soluble CD14 remained stable in both arms overtime.ConclusionLong-term (48-week) raltegravir intensification failed to counterbalance CD4 T-cell deficiency and its associated features: hyperactivation and death of CD4 T cells. However, raltegravir induced a specific reduction of CD38 expression in CD8 T cells, suggesting a beneficial effect on CD8 T-cell hyperactivation, which has been linked with HIV-associated comorbidities.

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