Impaired CD4+ T-cell and CD4+/CD8+ ratio recovery among people with HIV on antiretroviral therapy: prevalence and risk factors

Objective: Antiretroviral therapy (ART) decreases HIV viral replication leading to CD4+ recovery, decreased CD8+ expansion and CD4+/CD8+ ratio recovery. We investigated factors associated with impaired recovery of CD4+ and CD4+/CD8+ ratios among people with HIV (PWH) maintaining HIV viral suppression. Design/methods: PWH ≥18 years accessing the Southern Alberta Clinic between 01/01/1998-01/06/2022 entered the study at time of HIV viral suppression (<200 copies/mL). Continuous time-to-event Cox proportional hazard models estimated crude and adjusted hazards ratios (aHR) and 95% confidence intervals for factors associated with recovery of CD4+ count (≥500 cells/mm3) and CD4+/CD8+ ratio (≥1) at 10 years. Results: Over 10 years, 83% of PWH reached a CD4+ count of ≥500 cells/mm 3 but only 54% reached a CD4+/CD8+ ratio of ≥1. CD4+ recovery was less common among people diagnosed with HIV >50 years old vs. <30 years old (aHR: 0.59 [0.46-0.77]). Females were more likely to recover both CD4+ (aHR: 1.42[1.18–1.71]) and CD4+/CD8+ ratios (aHR: 1.56[1.25–1.95]) compared with males. Both higher baseline CD4+ counts and CD4+/CD8+ ratios were associated with greater immune recovery. ART regimen at study entry impacted CD4+ but not CD4+/CD8+ ratio recovery. CMV coinfection was associated with reduced CD4+/CD8+ ratio recovery (aHR: 0.47 [0.37–0.62]). Conclusions: While most PWH with ongoing viral suppression will recover their CD4+ cell counts, recovery of CD4+/CD8+ ratio recovery is less common, indicating ongoing immune dysfunction. Several demographic and clinical factors are associated with impaired immune recovery. Further characterization and understanding of the long-term impact of impaired immune recovery is needed.