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/mu L. Compared to participants with CD8 counts between 500/mu L and 1499/mu L, those with >1500/mu L 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/mu L (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. Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

Increased CD8 counts during treated HIV are related to immunosenescence, but the additional predictive values of CD8 counts and CD4/CD8 ratio to identify individuals with higher risk of clinical events in HIV remain controversial. Patients with CD8 counts >1500/μL have a higher risk of clinical events during years 3-7, while CD4/CD8 ratio is not predictive of greater event risk.