Background:  While HAART reduces plasma HIV-1 viremia to undetectable levels, replication-competent viruses persist in a pool of infected resting CD4 T cells. Immune responses are not able to completely clear this latent reservoir, thus persisting immune activation. The aim of this study was to determine whether intensification of a stable HAART with the HIV-1 integrase inhibitor raltegravir (RAL) could reduce immunological activation in patients with persistent viral suppression.

Methods:  A prospective, randomized, controlled, open-label study was performed including 51 HIV⁺ subjects with a CD4 T cell count ≥400 cells/mL and an undetectable viral load (<50 copies/mL) for at least 1 year while on HAART. Patients were randomized to intensify (n = 34) with RAL (400 mg twice daily) during 48 weeks or to continue with their HAART (n = 18). Immune activation was assessed in fresh blood by multicolor flow cytometric analysis using the following combinations: CD45RA/CD31/CD38/CD3/CD4/CD8 and PD-1/HLA-DR/CD38/CD45RO/CD3/CD8 at baseline and weeks 2, 4, and 12. All data reported as mean ±SD.

Results:  There were no baseline differences among groups for sex, age, years of HIV infection, CD4 T cell count, PI or NNRTI use, or immune activation (defined as CD8⁺HLA-DR⁺CD38⁺). Baseline CD4 T cell count inversely correlated with immune activation (r = –0.32, p = 0.025), but was not associated with time of infection. No significant differences were observed from baseline to week 12 in each group for activated HLA-DR⁺CD38⁺ CD8 T cells (18±11 vs 21±12, p = 0.22 and 18±10 vs 17±9, p = 0.79 for baseline and week 12 in control and intensified groups, respectively). Other markers of immune activation potentially related to viral replication, such as the expression of CD38 in memory CD8 T cells (CD8⁺CD45RO⁺) and CD4 T cells (CD4⁺CD45RA^–), were similar all throughout the study. Moreover, intensified subjects did not show any significant difference in their levels of activated CD8 T (CD8⁺HLA-DR⁺CD38⁺) cells when compared to the control group at any point studied (19±10 vs 15±7, p = 0.19 at week 2, 17±9 vs 18±9, p = 0.81 at week 4 and 18±9 vs 21±12, p = 0.23 at week 12).

Conclusions:  Short-term (12 weeks) treatment intensification with RAL in virologically suppressed patients on a stable HAART did not induce significant changes in immune activation markers. The effect of longer intensification periods on immune activation remains unknown.