Expanding HIV clinical monitoring: the role of CD4, CD8, and CD4/CD8 ratio in predicting non-AIDS events

Abstract

Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear.

Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events.

Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/μL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/μL, a CD8 count ≥1500 cells/μL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk.

Interpretation: Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/μL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions.

Funding: This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.

Keywords: CD4/CD8 ratio; Cardiovascular event; HIV; Neoplasia; Non-AIDS events.

Fig. 1

Survival curves for each CD4/CD8 cut-off. Survival probability and odds ratio (95% CI) for each subgroup of participants. The outcome studied is the cumulative incidence of serious non-AIDS events. The baseline visit (month 0 of follow-up) corresponds to 24 months after antiretroviral therapy initiation. The OR of presenting a clinical event corresponds to the five-year follow-up period.

Fig. 2

Survival curves for each CD4+ cut-off. Survival probability and odds ratio (95% CI) for each subgroup of participants. The outcome studied is the cumulative incidence of serious non-AIDS events. The baseline visit (month 0 of follow-up) corresponds to 24 months after antiretroviral therapy initiation. The OR of presenting a clinical event corresponds to the five-year follow-up period.

Fig. 3

Survival curves for each CD4/CD8 cut-off among participants with CD4+ count ≥500 cells/μL. Survival probability and odds ratio (95% CI) for each subgroup of participants. The outcome studied is the cumulative incidence of serious non-AIDS events. The baseline visit (month 0 of follow-up) corresponds to 24 months after antiretroviral therapy initiation. The OR of presenting a clinical event corresponds to the five-year follow-up period.