Abstract
(1) Objective: To investigate changes in mortality rates and predictors of all-cause mortality as well as specific causes of death over time among HIV-positive individuals in the combination antiretroviral therapy (cART) era. (2) Methods: We analyzed all-cause as well as cause-specific mortality among the Austrian HIV Cohort Study between 1997 and 2014. Observation time was divided into five periods: Period 1: 1997–2000; period 2: 2001–2004; period 3: 2005–2008; period 4: 2009–2011; and period 5: 2012–2014. Mortality rates are presented as deaths per 100 person-years (d/100py). Potential risk factors associated with all-cause mortality and specific causes of death were identified by using multivariable Cox proportional hazard models. Models were adjusted for time-updated CD4, age and cART, HIV transmission category, population size of residence area and country of birth. To assess potential nonlinear associations, we fitted all CD4 counts per patient using restricted cubic splines with truncation at 1000 cells/mm3. Vital status of patients was cross-checked with death registry data. (3) Results: Of 6848 patients (59,704 person-years of observation), 1192 died: 380 (31.9%) from AIDS-related diseases. All-cause mortality rates decreased continuously from 3.49 d/100py in period 1 to 1.40 d/100py in period 5. Death due to AIDS-related diseases, liver-related diseases and non-AIDS infections declined, whereas cardiovascular diseases as cause of death remained stable (0.27 d/100py in period 1, 0.10 d/100py in period 2, 0.16 d/100py in period 3, 0.09 d/100py in period 4 and 0.14 d/100py in period 5) and deaths due to non-AIDS-defining malignancies increased. Compared to latest CD4 counts of 500 cells/mm3, lower CD4 counts conferred a higher risk of deaths due to AIDS-related diseases, liver-related diseases, non-AIDS infections and non-AIDS-defining malignancies, whereas no significant association was observed for cardiovascular mortality. Results were similar in sensitivity analyses where observation time was divided into two periods: 1997–2004 and 2005–2014. (4) Conclusions: Since the introduction of cART, risk of death decreased and causes of death changed. We do not find evidence that HIV-positive individuals with a low CD4 count are more likely to die from cardiovascular diseases.
Highlights
Life expectancy of HIV-positive individuals has increased as mortality rates have markedly declined because of the widely used combination antiretroviral therapy [1,2,3,4]
This study examines the prognostic value of a time-updated CD4 cell count to predict specific causes of death
The median duration of combination antiretroviral therapy (cART) of individuals ever on cART was 80.3 months, 80.9% of them had been on cART for at least nine months
Summary
Life expectancy of HIV-positive individuals has increased as mortality rates have markedly declined because of the widely used combination antiretroviral therapy (cART) [1,2,3,4]. The latest absolute CD4 count, is more closely associated with mortality than the baseline CD4 count [9,10,11] or the slope of the CD4 T-cell increase [12]. With an increased duration of the cART era, numerous reports have described a decline on mortality rates and a change in causes of death. While AIDS-related mortality remains an important cause of death, increasing numbers of death due to non-AIDS-defining conditions such as malignancies, infections, liver diseases and cardiovascular diseases were reported [13,14]
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