Many HIV positive people never achieve a CD4 recovery to >500 cells/mm3 on ART even after many years on treatment. The role of residual immune activation in this response is unknown and as statins have anti-inflammatory effects their potential to modify immune activation may be important.
At AIDS 2014, Laurence Weiss, of the Université Paris Descartes, Paris, presented a poster from the CESAR-IMEA trial investigating whether rosuvastatin can decrease cellular and soluble markers of immune activation in patients receiving ART.1
In this open label, phase II trial, patients were enrolled who had >2 years ART, with CD4 counts <500 cells/mm3 and viral loads <40 copies/mL. C-reactive protein had to be <10 mg/mL with no indication for statin use. Rosuvastatin (20 mg, once-daily) was administered for 3 months, followed by 3 months follow up. The primary outcome was change in the proportion of CD38+ HLA-DR+CD8+ T lymphocytes after 12 weeks. Mean CD4 count at baseline was 319 cells/mm3 [IQR 284-442].
Of 50 patients who enrolled in the study, 43 reached study endpoints.
There was no significant change in the proportion of CD38+HLA-DR+CD8+ T cells throughout the follow-up. Despite this, the investigators reported a significant decline in the proportion of CD38+CD8+ T cells between baseline and week 12 (p=0.001) that was sustained until week 24. There were significant decreases in the percentage of Ki67+CD4+ T cells at week 12 (p=0.048), in HLA-DR+CD4+ T cells (p=0.044) and soluble CRP levels (p= 0.047). No changes were observed in the other soluble activation markers: IL-6, sCD14 and D-dimer.
The researchers concluded that rosuvastatin added to ART could result in sustained decreases in CD8 T cell activation. However, the lack of any decrease in the main marker of T cell activation, expression of CD38 and HLA-DR on CD8 T cells, is a major concern with this conclusion.
Although CD38 expression decreased on all CD8 T cells, this has questionable significance in terms of reducing T cell activation. CD38 can be constitutively expressed by various T cells in the absence of activation, for example naive T cells. Therefore it is not, on its own, a reliable marker of T cell activation and must be paired with other activation markers such as HLA-DR or markers of memory phenotype.
The reduction in the percentage of CD8 T cells expressing CD38, in the absence of a reduction in the percentage of CD8 T cells expressing both CD38 and HLA-DR together, calls into question the ability of rosuvastatin to reduce T cell activation in this study.
Despite this, the observed reduction in Ki67 in CD4 T cells is slightly more encouraging.
Weis L et al. A pilot study of the impact of rosuvastatin administration on residual chronic immune activation under antiretroviral therapy: the CESAR-IMEA trial. AIDS 2014: 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract WEPE095.
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