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

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.

PWH at least 18  years old accessing the Southern Alberta Clinic between 01 January 1998 and 01 June 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 (CIs) for factors associated with recovery of CD4 + count (≥500 cells/μl) and CD4 + /CD8 + ratio (≥1) at 10 years.

Over 10 years, 83% of PWH reached a CD4 + count of at least 500 cells/μl but only 54% reached a CD4 + /CD8 + ratio of ≥1. CD4 + recovery was less common among people diagnosed with HIV older than 50 years vs. younger than 30 years [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 + cell counts and CD4 + /CD8 + ratios were associated with greater immune recovery. ART regimen at study entry impacted CD4 + but not CD4 + /CD8 + ratio recovery. Cytomegalovirus (CMV) coinfection was associated with reduced CD4 + /CD8 + ratio recovery [aHR: 0.47 (0.37-0.62)].

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.