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Drops in AIDS Deaths, Some non-AIDS
Deaths Parallel ART Expansion in British Columbia
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CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
Overall 2-year mortality and HIV-related mortality dropped across British Columbia as antiretroviral therapy (ART) expanded from 2001 through 2012 [1]. Deaths from chronic liver disease, cardiovascular disease, and suicide also fell significantly across the study period. But women had a 37% higher death risk than men.
ART deployment has a profound impact on AIDS mortality, but its impact on all-cause mortality and non-AIDS causes of death remains incompletely defined. To reach a better understanding of how ART affects all-cause and cause-specific mortality, researchers in British Columbia analyzed deaths among people enrolled in the provincial Drug Treatment Program from January 1, 2001 to December 31, 2012. Antiretroviral therapy and HIV care are free in British Columbia.
The study involved British Columbian residents 18 or older who began ART during the study period. Researchers identified deaths in six 2-year periods (2001-2002 to 2011-2012) by linking antiretroviral treatment records with data from the British Columbia Vital Statistics Agency. They used ICD-10 codes to identify causes of death.
The analysis focused on 8185 people who took ART, including 4412 who started their first antiretroviral regimen during the study period. Overall mortality dropped from 257 of 4002 Drug Treatment Program participants (6.4%) in 2001-2002 to 224 of 6244 (3.6%) in 2011-2012, a significant decline (P = 0.018 test for trend). HIV-related mortality fell from 3.9% in 2001-2002 to 0.9% in 2011-2012, also a significant decrease (P = 0.021).
In Drug Treatment Program participants, the same period saw significant declines in deaths from chronic liver disease (0.32% to 0.14%, P = 0.015), cardiovascular disease (0.4% to 0.08%, P = 0.021), and suicide (0.77% to 0%, P = 0.002). Deaths from other infections, chronic respiratory disease, and non-AIDS cancers did not fall over the study period.
A Cox proportional hazards model adjusted for age, gender, history of injection drug use, and adherence to ART determined that, compared with people who started ART in 2001-2002, those who started in each later 2-year period had a significantly lower risk of death, at the following adjusted hazard ratios (aHR) (and 95% confidence intervals) (P < 0.001):
-- 2003-2004: aHR 0.73 (0.56 to 0.96)
-- 2005-2006: aHR 0.6 (0.45 to 0.81)
-- 2007-2008: aHR 0.57 (0.42 to 0.77)
-- 2009-2010: aHR 0.54 (0.37 to 0.79)
-- 2011-2012: aHR 0.46 (0.23 to 0.9)
In the same adjusted model, women had a 37% higher death risk than men (aHR 1.37, 95% CI 1.09 to 1.72, P = 0.007) and people with a history of injection drug use had more than a doubled risk of death compared with others (aHR 2.57, 95% CI 2.01 to 3.28, P < 0.001). Every 10% better antiretroviral adherence lowered the death risk 16% (aHR 0.84, 95% CI 0.81 to 0.86, P < 0.001), as did every 100-cell higher pre-ART CD4 count (aHR 0.84, 95% CI 0.78 to 0.91, P < 0.001). Having AIDS before ART did not significantly raise the death risk (aHR 1.22, 95% CI 0.95 to 1.57, P = 0.124).
AIDS and non-AIDS improvements in mortality, the researchers observed, "parallel a secondary expansion of ART in British Columbia which suggests broader clinical benefits to HIV treatment expansion beyond classically defined HIV-related conditions." Of course this kind of an analysis can demonstrate statistically significant associations but not causality.
Reference
1. Cheung C, Ding E, Zhu J, et al. Expansion of ART and Progressive Declines in All-Cause Mortality in British Columbia, Canada. CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 559.
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