Background:
Mortality rates in people living with HIV (PLWH) have declined in recent years due to effective antiretroviral treatment (ART). Aging, coinfections, and comorbidities among PLWH may drive further changes in mortality.
Methods:
Mortality due to specific causes classified by the Coding Causes of Death in HIV (CoDe) methodology were investigated between 2012–19 among PLWH from the RESPOND cohort consortium. Age-standardized mortality rates were calculated over 2-year periods and age-adjusted Poisson models were used to compare mortality between periods. We also investigated all-cause mortality with multivariable Cox regression.
Results:
Among 33642 PLWH with 170084 person-years of follow-up (PYFU) (median PYFU 4.9; IQR 3.1–8.0), 1702 (5.1%) died. Crude all-cause mortality per 1000 PYFU decreased from 13.0 (95%CI 11.8–14.4) in 2012–13 to 8.4 (95%CI 7.7–9.3) in 2018–19. Median age increased from 2012–13 (44 years IQR 36—51) to 2018–19 (49 IQR 40—56) as did median age at death from 52 (IQR 45—62) to 56 (IQR 48—65). The leading cause of death across the entire period was non-AIDS defining malignancy (NADM): 2.18 per 1000 PYFU (95%CI 1.96—2.41). Age-adjusted Poisson regression showed statistically significant decreases in mortality from 2012—13 to 2018—19 for deaths due to NADM, AIDS, cardiovascular disease (CVD), and liver disease (figure). The proportion of deaths due to AIDS (13.1% to 7.9%) and liver-disease (11.0% to 4.9%) declined from 2012—13 to 2018—19, and increased due to NADM (16.5% to 22.5%) and CVD (7.6% to 9.9%), but with concomitant increase in deaths due to unknown/missing causes (18.8% to 30.6%). In multivariable analysis, the strongest predictor of all-cause mortality was current CD4 ≤350 cells/mm3 + HIV viral load (VL) >200 cp/mL: adjusted hazard ratio (aHR) 10.4, 95%CI 8.8–12.3, vs. CD4 ≥500 cells/mm3 + VL < 200 cp/mL. Other predictors were chronic kidney disease (aHR 1.45, 1.24—1.68), diabetes (aHR 2.32, 1.91—2.82), chronic untreated hepatitis C (HCV) (aHR 2.18, 1.88—2.54 vs. HCV antibody negative), and smoking (aHR 2.03, 1.71—2.39 current vs. never; 1.5, 1.25—1.79 previous vs. never).
Conclusions:
In the RESPOND cohort, the leading cause of death was NADM. Age-adjusted mortality rates from AIDS, NADM, CVD, and liver-related causes declined, especially 2012—13 to 2016—17; the role of other contributing factors will be explored further. All-cause mortality was strongly associated with modifiable risk factors, indicating areas for improvement.
Cause-specific standardized mortality rate (SMR) per 2-year period