Predictive value of CD8+ T cell and CD4/CD8 ratio at two years of successful ART in the risk of AIDS and non-AIDS events

Background: While increased CD8 counts and low CD4/CD8 ratio during treated HIV correlate with immunosenescence, their additional predictive values to identify individuals with HIV at higher risk of clinical events remain controversial.

Methods: We selected treatment-naive individuals initiating ART from ACTG studies 384, 388, A5095, A5142, A5202, and A5257 who had achieved viral suppression at year 2. We examined the effect of CD8+ T cell counts and CD4/CD8 at year 2 on the probability of AIDS and serious non-AIDS events in years 3-7. We used inverse probability weighting methods to address informative censoring, combined with multivariable logistic regression models.

Findings: We analyzed 5133 participants with a median age of 38 years; 959 (19%) were female, pre-ART median CD4 counts were 249 (Q1-Q3 91-372) cell/µL. Compared to participants with CD8 counts between 500/µL and 1499/µL, those with >1500/µL had a higher risk of clinical events during years 3-7 (aOR 1.75; 95%CI 1.33-2.32). CD4/CD8 ratio was not predictive of greater risk of events through year 7. Additional analyses revealed consistent CD8 count effect sizes for the risk of AIDS events and noninfectious non-AIDS events, but opposite effects for the risk of severe infections, which were more frequent among individuals with CD8 counts <500/µL (aOR 1.70; 95%CI 1.09-2.65).

Interpretation: The results of this analysis with pooled data from clinical trials support the value of the CD8 count as a predictor of clinical progression. People with very high CD8 counts during suppressive ART might benefit from closer monitoring and may be a target population for novel interventions.

Funding: This research was supported by NIH/NIAID awards UM1 AI068634, UM1 AI068636, and UM1 AI106701 and Carlos III Health Institute and FEDER funds (BA21/00017 and BA21/00022).