Long-term immune reconstitution patterns and influencing factors in people living with HIV exhibiting suboptimal immune response after 24 months of antiretroviral therapy.

OBJECTIVES

This study aimed to characterize long-term immune reconstitution trajectories and influencing factors in people living with HIV exhibiting suboptimal early immune responses after 24 months of antiretroviral therapy (ART).

METHODS

We conducted a retrospective multicentre study from January 2016 to October 2024. Eligible participants achieved sustained virological suppression within six months of ART but maintained CD4+ T cell counts <350 cells/μL at 24 months. Demographic and clinical characteristics were analysed, and Cox regression models were used to identify factors associated with different long-term immune reconstitution patterns.

RESULTS

Among 5272 virologically suppressed individuals, 348 were included in the final analysis. The median age was 48 years (IQR 38.0-57.0), and the median duration of ART was 4.5 years (IQR 4.0-6.0). The overall median CD4+ T cell counts increased gradually during the first four years after ART initiation, followed by an annual growth <10 cells/μL thereafter. Three distinct immune recovery trajectories were identified: progressively increasing (37.1%), minor fluctuating (56.9%) and progressively declining (6.0%). Among the increasing group, 62.0% eventually achieved immune reconstitution. Cox regression analysis showed that baseline CD4+ T cell counts ≥200 cells/μL were strongly associated with successful long-term immune reconstitution (HR = 1.9, 95% CI: 1.2-2.9), whereas transient viremia increased the risk of both fluctuating (HR = 2.3, 95% CI: 1.2-4.8) and declining trajectories (HR = 2.5, 95% CI: 1.1-6.0).

CONCLUSION

People living with HIV with suboptimal early immune responses exhibit three distinct immune recovery trajectories. Higher baseline CD4+ T cell levels favour long-term reconstitution, whereas transient viremia may predict persistent immune failure.