CD4:CD8 ratio is more sensitive marker of risk than CD4 counts in analysis from START study

An analysis from the START study reported that the CD4:CD8 ratio was a better predictor of risk compared to the CD4 count in people with strong immune function.

These START results showed that early antiretroviral treatment (ART) is protective against the primary endpoints of serious HIV- and non-HIV-related events that still occured at high CD4 counts. Understanding whether there are more sensitive markers than the CD4 count could both help identify people at higher risk and have the potential to change the way HIV is routinely monitored now that ART is increasingly started at high CD4 counts.

START randomised more the 4600 treatment naive participants with CD4 counts above 500 to either immediate ART or deferring until the CD4 count reached 350. This analysis looked at hazard ratios (HR) for individual biomarkers and combinations including CD4, CD8, CD4%, CD8%, CD4:CD8 ratio and HIV viral load, with and without adjustment of other baseline variables (including age, gender, country etc).

In the 138 people with serious events over three years, the absolute CD4 count had no association with risk of a serious event in the early ART group (HR per 100 cells higher 0.98; 95%CI: 0.88 to 1.11, p = 0.78) and only a moderate association in the group with deferred ART (HR 0.87; 95%CI: 0.79 to 0.97, p=0.011).

However, CD8, CD8%, CD4:CD8 ratio and viral load were strong predictors irrespective of treatment group: HR 1.07 (CI:1.04,1.09, p<0.001) per 100 CD8 cells higher and 0.85 (CI: 0.80,0.90, p<0.001) per 20% higher CD4:CD8 ratio. The effect of CD8 count and CD4:CD8 ratio remained strong after adjusting for viral load (p<0.001 and p<0.002, respectively).

Further analyses showed that although reduction in viral load explained most of the reduced risk of serious events, this was also to a lesser extent linked to an increase in CD4:CD8 ratio.

Comment

The finding that CD8 and CD4:CD8 ratio were better predictors of serious events is an important result for monitoring people at high CD4 counts.

This warrants review by guidelines that have already moved to reducing immunological monitoring with CD4 counts in people who are assumed to be at low risk.

Babiker A et al. The role of plasma HIV RNA and T cell subset counts/percent and ratio in explaining the benefit of immediate antiretroviral therapy (ART) initiation in HIV+ individuals with high CD4+ counts. AIDS2016. Durban, South Africa. 18-22 July 2016. Poster abstract THPEB054.
http://programme.aids2016.org/Abstract/Abstract/7083