A Randomized, Controlled Trial of Raltegravir Intensification in Antiretroviral-treated, HIV-infected Patients with a Suboptimal CD4+ T Cell Response

Highly active antiretroviral therapy (HAART) has been effective in decreasing morbidity and mortality associated with human immunodeficiency virus (HIV) infection [1]. However, a significant proportion of individuals are unable to achieve a normal CD4+ T cell count despite prolonged viral suppression with effective HAART. In one study, ∼25% of patients who started HAART at a CD4+ T cell count of 500 cells/mm3 even after more than 7–10 years of HAART [2]. Moreover, having a suboptimal CD4+ T cell response has been associated with significant clinical consequences, including increased AIDS-related and non–AIDS-related morbidity and mortality [3–6]. The mechanisms of suboptimal immune recovery are not completely understood. Persistent T cell activation may be causally related to the inability to reconstitute normal CD4+ T cell counts, perhaps owing to its effect on lymphoid tissue architecture [7–11]. Moreover, ongoing low-level viral replication may be the proximal cause of persistent activation during HAART [12–15]. Several studies have attempted to address this issue [15–18], although none have focused on the host responses to HIV in both blood and gut-associated lymphoid tissue (GALT). We conducted a randomized, double-blinded, placebo-controlled study of raltegravir intensification to assess whether ongoing viral replication contributes to immune activation and suboptimal immune recovery during HAART. Our secondary objective was to explore the host determinants of viral persistence in both blood and GALT.