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Plasma Soluble CD163 Level Independently Predicts All-Cause Mortality in HIV-1-Infected Individuals
Troels Bygum Knudsen1, Gideon Ertner1, Janne Petersen2
1Department of Infectious Diseases.
Insights
Elevated soluble CD163 (sCD163) levels in HIV-1 patients predict increased mortality risk. This finding suggests that monocyte and macrophage activation are key factors in HIV disease progression and potential therapeutic targets.
Area of Science:
- Immunology
- Virology
- Clinical Medicine
Background:
- CD163 is a scavenger receptor found on monocytes and macrophages.
- Soluble CD163 (sCD163) is released during inflammation.
- The role of sCD163 in HIV-1 infection progression and mortality is not fully understood.
Purpose of the Study:
- To investigate the association between plasma sCD163 levels and the risk of AIDS progression and all-cause mortality in individuals with HIV-1 infection.
Main Methods:
- Plasma sCD163 levels were measured in 933 individuals with HIV-1.
- Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.
Main Results:
- Higher plasma sCD163 levels were observed in non-survivors compared to survivors (4.92 mg/L vs. 3.16 mg/L, P = .0001).
- An increase of 1 mg/L or one quartile in baseline plasma sCD163 level was associated with a 6% or 35% increased risk of death, respectively (adjusted HRs: 1.06 and 1.35).
Conclusions:
- Plasma sCD163 is an independent predictor of all-cause mortality in HIV-1 infected individuals.
- Monocyte and macrophage activation may contribute to HIV pathogenesis.
- Targeting monocyte/macrophage activation could be a potential therapeutic strategy for HIV-1 infection.
Background:
CD163, a monocyte- and macrophage-specific scavenger receptor, is shed as soluble CD163 (sCD163) during the proinflammatory response. Here, we assessed the association between plasma sCD163 levels and progression to AIDS and all-cause mortality among individuals infected with human immunodeficiency virus type 1 (HIV).
Methods:
Plasma sCD163 levels were measured in 933 HIV-infected individuals. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with mortality were computed by Cox proportional hazards regression.
Results:
At baseline, 86% were receiving antiretroviral treatment, 73% had plasma a HIV RNA level of <50 copies/mL, and the median CD4(+) T-cell count was 503 cells/µL. During 10.5 years of follow-up, 167 (17.9%) died. Plasma sCD163 levels were higher in nonsurvivors than in survivors (4.92 mg/L [interquartile range {IQR}, 3.29-8.65 mg/L] vs 3.16 mg/L [IQR, 2.16-4.64 mg/L]; P = .0001). The cumulative incidence of death increased with increasing plasma sCD163 levels, corresponding to a 6% or 35% increased risk of death for each milligram per liter or quartile increase, respectively, in baseline plasma sCD163 level (adjusted HR, 1.06 [95% CI, 1.03-1.09] and 1.35 [95% CI, 1.13-1.63], respectively).
Conclusions:
Plasma sCD163 was an independent marker of all-cause mortality in a cohort of HIV-infected individuals, suggesting that monocyte/macrophage activation may play a role in HIV pathogenesis and be a target of intervention.
