Objective(s): We investigated the probability of transitioning in or out of the CD3+ T-cell homeostatic range during antiretroviral therapy, and we assessed the clinical impact of lost T-cell homeostasis (TCH) on AIDS-defining illnesses (ADIs) or death.
Design: Within the Canadian Observational Cohort (CANOC), we studied 4463 antiretroviral therapy (ART)-naive HIV-positive patients initiating combination ART (cART) between 2000 and 2010.
Methods: CD3+ trajectories were estimated using a four state Markov model. CD3+ T-cel percentage states were classified as follows: very low (<50%), low (50–64%), normal (65–85%), and high (>85%). Covariates associated with transitioning between states were examined. The association between CD3+ T-cell percentage states and time to ADI/death from cART initiation was determined using Cox proportional hazards models.
Results: A total of 4463 patients were followed for a median of 3 years. Two thousand, five hundred and eight (56%) patients never transitioned from their baseline CD3+ T-cell percentage state; 85% of these had normal TCH. In multivariable analysis, individuals with time-updated low CD4+ cell count, time-updated detectable viral load, older age, and hepatitis C virus (HCV) coinfection were less likely to maintain TCH. In the multivariable proportional hazards model, both very low and high CD3+ T-cell percentages were associated with increased risk of ADI/death [adjusted hazard ratio=1.91 (95% confidence interval, CI: 1.27–2.89) and hazard ratio=1.49 (95% CI: 1.13–1.96), respectively].
Conclusion: Patients with very low or high CD3+ T-cell percentages are at risk for ADIs/death. To our knowledge, this is the first study linking altered TCH and morbidity/mortality in cART-treated HIV-positive patients.