Association of leukocyte count with death in people with HIV: A longitudinal study over 24 years

Objectives: Increased blood leukocytes are associated with all-cause mortality and death from coronary disease and cancer in the general population. Limited information is available in people with HIV. Methods: We analyzed blood leukocytes in 1850 participants of the Swiss HIV Cohort Study who died (2000-2023) and 1850 matched controls (median age at death 52 years, 77% male, 77% with suppressed HIV RNA on antiretroviral therapy). We assessed uni-/multivariable odds ratios (OR) for all-cause mortality, considering major clinical and HIV-related mortality risk factors, leukocytes measured >1 year before death (primary analysis) and in the latest available blood sample, and potential confounders for leukocytes. Results: Leukocytes showed a U-shaped association with mortality. At a median of 433 (interquartile range [IQR], 396-495) days before death, multivariable-adjusted OR for death in the highest (leukocytes ≥7730/μL) vs. middle quintile (leukocytes 5290-6260/μL) was 1.56 (95% confidence interval, 1.20-2.02). Multivariable-adjusted OR in the lowest (leukocytes ≤4250/μL) vs. middle leukocyte quintile was 1.51 (1.14-2.01). For comparison, death-OR for hypertension, diabetes and current smoking were 1.27 (1.06-1.53), 1.91 (1.41-2.57), and 2.72 (2.14-3.45), respectively. Leukocytosis was uncommon (cases, 4.4% vs. controls, 2.3%; p = 0.004). The effect size of the highest leukocyte quintile increased in the latest blood sample (median 86 [IQR], 43-152 days before death; OR=1.99 [1.44-2.76]). High leukocytes were associated with death from non-AIDS/non-hepatic cancer, cardiovascular, and respiratory causes. Low leukocytes were associated with liver-related death. Conclusions: High leukocytes, measured >1 year before death and mostly within the normal range, are independently associated with mortality in people with HIV in Switzerland.