Clinical events associated with poor CD4(+) T-cell recovery in people living with HIV following ART: A systematic review and meta-analysis

Background: Antiretroviral therapy (ART) has significantly improved outcomes for people living with HIV (PLWH), but poor CD4⁺ T-cell recovery remains a challenge. This study aimed to evaluate the relationship between poor CD4⁺ T-cell recovery and the morbidity of clinical events (CEs) in PLWH after ART initiation.

Methods: We conducted a comprehensive search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases up to February 19, 2024, and included studies that reported the number of CEs along with the CD4 count at the time of the CEs or the most recent CD4 count prior to the CEs. A random-effects model was employed for meta-analysis to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for CEs at different CD4 count thresholds.

Findings: We included 15 studies with 54,766 PLWH and reported a significant inverse correlation between CD4⁺ T-cell counts and the morbidity of both AIDS-defining events (ADEs) and non-AIDS-defining infections (NADIs). However, CD4⁺ T-cell counts were not significantly associated with non-AIDS-defining noninfections (NADNIs). Compared with individuals with normal CD4 counts (>500 cells/μL), those with CD4 counts <200 cells/μL and 200–350 cells/μL exhibited higher ADEs morbidity, with ORs of 7·04 (95% CI: 1·77–28·03) and 1·63 (95% CI: 1·36–1·97), respectively. Similarly, individuals with CD4 counts <200 cells/μL showed a higher morbidity of NADIs (OR = 2·82, 95% CI: 1·50–5·31). However, no significant difference in NADNI morbidity was observed between groups with poor CD4⁺ T-cell recovery and those with normal CD4 counts.

Interpretation: This meta-analysis revealed an inverse relationship between CD4⁺ T-cell counts and morbidity associated with ADEs and NADIs in PLWH after ART initiation, with key thresholds of 350 cells/μL and 200 cells/μL. No significant associations were found between CD4 counts and NADNIs. These results highlight the need for comprehensive patient care that goes beyond monitoring only CD4 counts.

• Population(s)
  • General HIV+ population
• Prevention, Engagement and Care Cascade
  • Engagement and Care Cascade
• Engagement and Care Cascade
  • Linkage/engagement in care
  • Retention in care
  • Treatment
• Health Systems
  • Delivery arrangements