{"id":27461,"date":"2014-10-01T12:31:26","date_gmt":"2014-10-01T12:31:26","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=27461"},"modified":"2014-10-06T11:26:35","modified_gmt":"2014-10-06T11:26:35","slug":"rosuvastatin-may-be-partially-effective-in-moderating-residual-immune-activation-on-art","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/27461","title":{"rendered":"Rosuvastatin may be partially effective in moderating residual immune activation on ART"},"content":{"rendered":"

Gareth Hardy, HIV i-Base<\/strong><\/p>\n

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.<\/strong><\/p>\n

At AIDS 2014, Laurence Weiss, of the Universit\u00e9 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]<\/p>\n

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].<\/p>\n

Of 50 patients who enrolled in the study, 43 reached study endpoints.<\/p>\n

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.<\/p>\n

Comment<\/h3>\n

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.<\/strong><\/p>\n

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.<\/strong><\/p>\n

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.<\/strong><\/p>\n

Despite this, the observed reduction in Ki67 in CD4 T cells is slightly more encouraging.<\/strong><\/p>\n

Reference:<\/p>\n

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.
\nhttp:\/\/pag.aids2014.org\/abstracts.aspx?aid=7710<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Gareth Hardy, HIV i-Base 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 …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,8],"tags":[191],"class_list":["post-27461","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-side-effects","tag-aids-20th-melbourne-2014"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/27461","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=27461"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/27461\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=27461"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=27461"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=27461"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}