Association of leukocyte count with death in people with HIV: A longitudinal study over 24 years
In a recent study published in PLoS One, Klein et al. investigated whether total leukocyte count predicts mortality in people living with HIV enrolled in the Swiss HIV Cohort Study. Although antiretroviral therapy has markedly improved survival, excess mortality persists, and chronic inflammation is thought to contribute to long-term risk. Because leukocyte count is routinely measured and inexpensive, the authors examined its long-term prognostic value.
The analysis included 1’850 participants who died between 2000 and 2023 and 1’850 matched controls. Leukocyte counts measured one to five years before death were evaluated, with adjustment for demographic factors, traditional cardiovascular risk factors, smoking, comorbidities, CD4 cell count, viral suppression status, and other HIV-related variables. Most participants were middle-aged, predominantly male, and the majority were virologically suppressed.
A U-shaped association between leukocyte count and mortality was observed. Compared with individuals in the middle leukocyte quintile, both low leukocyte counts (≤4’250/µL) and high leukocyte counts (≥7’730/µL) were independently associated with increased odds of death. Importantly, most elevated leukocyte values were within the normal laboratory range, and overt leukocytosis was uncommon. The association between high leukocyte counts and mortality remained robust across multiple sensitivity analyses, including among participants with suppressed viral load.
Cause-specific analyses showed that higher leukocyte counts were associated with death from non-AIDS, non-hepatic cancers, cardiovascular causes, and respiratory disease, whereas low leukocyte counts were associated with liver-related and AIDS-related mortality, largely reflecting advanced immunosuppression.
In summary, the study demonstrates that both low and high leukocyte counts predict mortality in people with HIV, even when measured years before death and often within normal ranges. These findings suggest that routine leukocyte measurements may provide additional prognostic information and reflect clinically relevant inflammatory risk in treated HIV infection.