Identifying Longitudinal CD4:CD8 Ratio Trajectories Indicative of Chronic Renal Disease Risk among People Living with HIV: An Application of Growth Mixture Models

The incidence of chronic kidney disease (CKD) is increasing among people living with HIV (PLWH). Routine monitoring of indicators such as CD4:CD8 ratio might improve the early detection of CKD. Our objective was to identify clinically relevant CD4:CD8 ratio trajectories indicative of CKD risk. Participants were ≥ 18 years old, initiated antiretroviral therapy between 2000 and 2016, and were followed for ≥6 months until 31 March 2017 or last contact date. Outcome was incidence of CKD. Growth mixture models (GMMs) and decay models were used to compare CD4:CD8 ratio trajectories. Following GMM, 4547 (93.5%) participants were classified in Class 1 with 5.4% developing CKD, and 316 (6.5%) participants were classified in Class 2 with 20.9% developing CKD. The final model suggested that participants in Class 2 had 8.72 times the incidence rate of developing CKD than those in Class 1. Exponential decay models indicated a significant CD4:CD8 ratio decline among Class 2 participants who developed CKD. Among those who developed CKD in Class 2, starting at 5.5 years of follow-up, the slope of their ratio trajectory curve changed significantly, and the rate of decline increased dramatically. Routine monitored CD4:CD8 ratios can be an effective strategy to identify early CKD risk among PLWH.