Longitudinal evolution and risk profiles of comorbidity among people with HIV in China: a retrospective cohort study.

Objective: With increased longevity among people with HIV (PWH), multimorbidity has become a major challenge, but its long-term evolution remains poorly described. We aimed to characterize the longitudinal evolution of comorbidity and identify risk profiles for metabolic and mixed infectious-non-infectious multimorbidity among PWH initiating antiretroviral therapy in China. Methods: We conducted a retrospective cohort study of 5,950 PWH initiating antiretroviral therapy (ART) in Shenzhen, China (2009-2016), with follow-up through 2024. Twenty-six predefined comorbid conditions were classified as curable or incurable. Multimorbidity was defined as ≥2 conditions and grouped into six mutually exclusive comorbidity states. Evolution over 8 years was described using Sankey diagrams and stratified analyses. Multivariable Cox and logistic regression models were used to identify risk factors for incident metabolic multimorbidity and mixed infectious-non-infectious multimorbidity. Results: At ART initiation, 25.9% of participants had multimorbidity; by year 8 this had increased to 42.5%, mainly due to incurable multimorbidity (7.7 to 25.5%). Among 1,464 participants free of all 26 conditions at baseline, 36.1% developed multimorbidity. Younger PWH (≤ 32 years) experienced a steeper decline in comorbidity-free status, whereas older participants (≥46 years) were more likely to accumulate incurable multimorbidity. Dyslipidemia was the earliest and most persistent comorbidity and formed the core of the most frequent multimorbidity clusters. In the metabolic model, older age (≥46 vs. ≤ 25 years; hazard ratio [HR] 3.42, 95% confidence interval [CI] 2.60-4.49), higher body mass index (BMI), male sex, elevated fasting glucose, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen and reduced estimated glomerular filtration rate (eGFR) were associated with increased risk. For mixed infectious-non-infectious multimorbidity, male sex, injection drug use (IDU), low CD4 count, thrombocytopenia and opportunistic infections were risk factors, whereas higher BMI and being married were protective. Conclusion: Among relatively young Chinese PWH, multimorbidity increases rapidly after ART initiation, driven by metabolic and other incurable conditions centered on dyslipidemia. Distinct risk profiles for metabolic and mixed infectious-non-infectious patterns support integrating early cardiometabolic screening, intensifying infection control and proactive management of dyslipidemia into routine HIV care.