Antiretroviral therapy (ART) and gains in life expectancy have increased the likelihood of people living with HIV (PLWH) developing comorbidities. We examined which chronic comorbidities, experienced in isolation or in combination, led to higher mortality rates among PLWH compared to HIV-negative controls. Secondarily, we assessed the impact of multimorbidity on all-cause mortality among PLWH.
This population-based cohort study used longitudinal individual-level data on all treated PLWH and 1:5 age-sex-matched HIV-negative controls in British Columbia (BC), Canada. Eligible participants were ≥19 years old and enrolled in the Comparative Outcomes and Service Utilization Trends Study between 2001 and 2012 for ≥1 year. Comorbidities were identified from provincial administrative health databases (i.e., hospitalizations, outpatient physician, and pharmacy records). Selected comorbidities included liver, cardiovascular (CVD), renal, non-AIDS-defining cancers (NADC), hypertension, diabetes, and chronic obstructive pulmonary disease. Marginal structural models estimated the risk of all-cause mortality among PLWH with 1, 2 and ≥3 comorbidities (versus none).
Overall, 51% of 8,405 PLWH, and 30% of 42,025 HIV-negative individuals developed ≥1 comorbidity by the end of follow-up. With the exception of the CVD-NADC combination, PLWH had higher all-cause mortality rates for all singular and combinations of diseases (see Figure). The largest disparity in mortality rate was related to renal disease (in isolation), where PLWH had a rate >30 times higher than that of HIV-negative controls. Among PLWH and the HIV-negative controls, a liver-NADC combination was associated with the highest mortality rate per 1000 person-years: 106.6 (95% confidence interval: 73.57-139.64) and 78.2 (46.24-110.16), respectively. After adjustment for demographic and time-dependent treatment-related confounders, PLWH with 1, 2 and ≥3 comorbidities were, respectively, 3.15 (2.57-3.86), 5.95 (4.65-7.61) and 12.96 (15.59-40.80) times more likely to die than PLWH without comorbidities.
Compared to HIV-negative controls, after adjusting for similar morbidities, PLWH experienced substantial excess in mortality rates. Additionally, we observed a strong positive dose-response between the number of morbidities and the risk of mortality among PLWH. These results highlight the critical role that additional morbidities continue to pose as drivers of mortality among PLWH within a publicly funded province-wide ART program.