More on the Links Between the CD4/CD8 Ratio, Immunological Perturbations, and Risk of Illness and Death

May 21, 2014

Since posting recently about studies investigating the relevance of the CD4/CD8 ratio in the antiretroviral therapy era, several new papers and presentations have provided more information on the topic. Last week 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 naive CD8 T cells, elevated levels of activated and senescent CD8 T cells, increased innate immune activation, and a greater risk of non-AIDS events. 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. 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.

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. 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. 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.

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. Additionally, HIV-positive individuals on suppressive ART who do not experience an increase in the CD4/CD8 ratio "might benefit from screening programs or aggressive management of concomitant risk factors for aging-associated disease."

Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.

This article was provided by Treatment Action Group. It is a part of the publication Michael Palm HIV Basic Science, Vaccines & Cure Project.

No comments have been made.

Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read's Comment Policy.)

Your Name:

Your Location:

(ex: San Francisco, CA)

Your Comment:

Characters remaining:


The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.