Combining CD4 count, CD8 count and CD4/CD8 ratio to predict risk of mortality among HIV-positive adults after therapy: a group-based multi-trajectory analysis.

Introduction: Previous studies have indicated different immunological recovery trajectories based on CD4 count or CD4/CD8 ratio. However, these immune indicators are interconnected, and relying solely on one indicator may lead to inaccurate estimates. Therefore, it is essential to develop a comprehensive trajectory model that integrates CD4 count, CD8 count and CD4/CD8 ratio.

Methods: We utilized a group-based multi-trajectory model to characterize the latent cluster of recovery based on measurements of CD4 count, CD8 count and CD4/CD8 ratio over a period of up to 96 months following ART initiation. Subsequently, we investigated the characteristics associated with trajectory groups, especially sex and age. Cox model and Kaplan-Meier survival curve were employed to assess differences in all-cause, AIDS-related and non-AIDS related mortality between trajectory groups.

Results: A total of 14,718 eligible individuals were followed for a median of 55 months. Longitudinal model identified four subgroups: group 1 (32.5%, low CD4 and CD4/CD8 inversion), group 2 (25.9%, high CD8 and CD4/CD8 inversion), group 3 (27.2%, slow recovery of CD4 and CD4/CD8 inversion) and group 4 (14.4%, rapid increase of CD4 and normal CD4/CD8). Immune recovery was slower in male than in female, and in elders than in youngers. Compared to group 2, group 1 (adjusted hazard ratio [aHR]=3.28; 95% CI 2.33-4.60) and group 3 (aHR=1.56; 95% CI 1.09-2.24) had increased risk of all-cause mortality after adjusting for other factors. Besides, group 1 (aHR=2.17) and group 3 (aHR=1.58) had higher risk of non-AIDS related mortality, and group 1 (aHR=5.92) had significantly increased risk of AIDS related mortality.

Conclusion: Longitudinal trajectory analysis of multiple immune indicators can be employed to guide targeted interventions among vulnerable populations in clinical practice.