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

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.