Background . The CD4 T cell count recovery in human immunodeficiency virus type 1 (HIV-1)—infected individuals receiving potent antiretroviral therapy (ART) shows high variability. We studied the determinants and the clinical relevance of incomplete CD4 T cell restoration.

Methods . Longitudinal CD4 T cell count was analyzed in 293 participants of the Swiss HIV Cohort Study who had had a plasma HIV-1 RNA load <1000 copies/mL for ⩾5 years. CD4 T cell recovery was stratified by CD4 T cell count 5 years after initiation of ART (⩾500 cells/µL was defined as a complete response, and <500 cells/µL was defined as an incomplete response). Determinants of incomplete responses and clinical events were evaluated using logistic regression and survival analyses.

Results . The median CD4 T cell count increased from 180 cells/µL at baseline to 576 cells/µL 5 years after ART initiation. A total of 35.8% of patients were incomplete responders, of whom 47.6% reached a CD4 T cell plateau <500 cells/µL. Centers for Disease Control and Prevention HIV-1 disease category B and/or C events occurred in 21% of incomplete responders and in 14.4% of complete responders (P > .05). Older age (adjusted odds ratio [aOR], 1.71 per 10-year increase; 95% confidence interval [CI], 1.21–2.43), lower baseline CD4 T cell count (aOR, 0.37 per 100-cell increase; 95% CI, 0.28–0.49), and longer duration of HIV infection (aOR, 2.39 per 10-year increase; 95% CI, 1.19–4.81) were significantly associated with a CD4 T cell count <500 cells/µL at 5 years. The median increases in CD4 T cell count after 3–6 months of ART were smaller in incomplete responders (P < .001) and predicted, in conjunction with baseline CD4 T cell count and age, incomplete response with 80% sensitivity and 72% specificity.

Conclusion . Individuals with incomplete CD4 T cell recovery to <500 cells/µL had more advanced HIV-1 infection at baseline. CD4 T cell changes during the first 3–6 months of ART already reflect the capacity of the immune system to replenish depleted CD4 T lymphocytes.