{"id":25838,"date":"2014-05-27T12:06:24","date_gmt":"2014-05-27T12:06:24","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=25838"},"modified":"2017-02-20T09:31:01","modified_gmt":"2017-02-20T09:31:01","slug":"more-on-the-links-between-the-cd4cd8-ratio-immunological-perturbations-and-risk-of-illness-and-death","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/25838","title":{"rendered":"More on the links between the CD4\/CD8 ratio, immunological perturbations, and risk of illness and death"},"content":{"rendered":"

Richard Jefferys, TAG<\/strong><\/p>\n

Since the review in the last issue of HTB of studies investigating the relevance of the CD4\/CD8 ratio in the antiretroviral therapy era,<\/strong> [1] several new papers and presentations have provided more information on the topic. <\/strong><\/p>\n

In the open access journal PLoS Pathogens, Sergio Serrano-Villar and colleagues reported evidence that a low CD4\/CD8 ratio (less than or equal to 0.4) – despite CD4 T cell recovery to a count above 500 on ART – is associated with low na\u00efve CD8 T cells, elevated levels of activated and senescent CD8 T cells, increased innate immune activation, and a greater risk of non-AIDS events. [2]<\/p>\n

After controlling for age, gender, ART duration and both nadir and proximal CD4 count, each 10% decrease in the CD4\/CD8 ratio was associated with 48% higher odds of serious non-AIDS events.<\/p>\n

In a separate cohort that started ART with advanced disease, a significant correlation between the CD4\/CD8 ratio and the risk of mortality was documented. In this analysis, the researchers report that for each 10% increase in the CD4\/CD8 ratio on ART there was a 15% decrease in the risk of death. Individuals initiating ART earlier in the course of HIV infection exhibited greater and more rapid improvements in the CD4\/CD8 ratio compared to those starting late.<\/p>\n

A poster at CROI 2014 presented similar findings. Cristina Mussini and colleagues assessed whether the CD4\/CD8 ratio predicted clinical progression in the Icona cohort in Italy. The CD4\/CD8 ratio was a significant predictor of the risk of serious non-AIDS events and death, independent of CD4 T cell counts. Normalization of the CD4\/CD8 ratio (to greater than or equal to 1) only occurred in a minority of participants, and was more common among younger individuals, those with higher CD4\/CD8 ratios at ART initiation, and those starting ART in more recent periods at higher CD4 T cell counts. [3]<\/p>\n

Another poster at CROI from Talia Sainz et al described the role of CMV infection in lowering CD4\/CD8 ratios in HIV-positive people, as is also known to occur in the HIV negative elderly. [4]<\/p>\n

Lastly, a recent paper in PLoS One published by Willard Tinago and colleagues from the laboratory of Paddy Mallon in Dublin looked at the links between the CD4\/CD8 ratio and other immunological perturbations, with results that appear consistent with those reported by Sergio Serrano-Villar’s group. [5]<\/p>\n

The discussion section of the Serrano-Villar paper notes that the data imply that the CD4\/CD8 ratio could be useful for monitoring responses to therapies that aim to reduce residual immune activation.<\/p>\n

Additionally, HIV positive individuals on suppressive ART who do not experience an increase in the CD4\/CD8 ratio “might benefit from screening programmes or aggressive management of concomitant risk factors for ageing-associated disease.”<\/p>\n

Source:<\/p>\n

TAG Basic Science Blog. Update published on the first Berlin patient. (21 May 2014).<\/p>\n

http:\/\/tagbasicscienceproject.typepad.com<\/a><\/p>\n

References:<\/p>\n

    \n
  1. Jefferys R. The relevance of the CD4\/CD8 ratio in the ART era. HIV Treatment Bulletin (HTB) March\/April 2014.https:\/\/i-base.info\/htb\/24837<\/a><\/li>\n
  2. Serrano-Villar S et al. HIV-infected individuals with low CD4\/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.PLoS Pathog. 2014 May 15;10(5):e1004078. doi: 10.1371\/journal.ppat.1004078.<\/li>\n
  3. Mussini C et al. Incidence of CD4\/CD8 ratio normalization and its role in the onset of non-AIDS-related events. Conference on Retroviruses and Opportunistic Infections, March 3-6 2014, Boston, MA CROI 2014. Poster abstract 753.http:\/\/croiconference.org\/sites\/all\/abstracts\/753.pdf<\/a> (PDF)<\/li>\n
  4. Sainz T et al. CMV and HIV: A Double Hit On the CD4\/CD8 Ratio. Conference on Retroviruses and Opportunistic Infections, March 3-6 2014, Boston, MA CROI 2014. Postar abstract 243.http:\/\/croiconference.org\/sites\/all\/abstracts\/243.pdf<\/a> (PDF)<\/li>\n
  5. Tinago W et al. Clinical, immunological and treatment-related factors associated with normalised CD4+\/CD8+ T-cell ratio: effect of na\u00efve and memory T-cell subsets. PLoS One. 2014 May 9;9(5):e97011. doi: 10.1371\/journal.pone.0097011.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Richard Jefferys, TAG Since the review in the last issue of HTB of studies investigating the relevance of the CD4\/CD8 ratio in the antiretroviral therapy era, [1] several new papers and presentations have provided more information on the topic. In …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20,15],"tags":[],"class_list":["post-25838","post","type-post","status-publish","format-standard","hentry","category-cure-research","category-basic-science-and-immunology"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/25838","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=25838"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/25838\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=25838"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=25838"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=25838"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}