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  Conference on Retroviruses
and Opportunistic Infections
Seattle, Washington
Feb 19-22 2023
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Rates of Key Death Causes With HIV Falling in Europe/America. Deaths Due to Comorbidities
  30th CROI, Conference on Retroviruses and Opportunistic Infections, February 19-22, 2023, Seattle
Mark Mascolini
Rates of many major causes of death dwindled among adults with HIV in Europe and North America from 1996 through 2020 [1]. Antiretroviral Therapy Cohort Collaboration (ART CC) researchers who conducted this analysis believe their findings underline the importance of vigilant screening for and treatment of comorbidities including cardiovascular disease, cancer, and psychiatric disorders.
ART CC investigators noted that several factors may contribute to changing death rates in HIV populations-stronger antiretroviral therapy, aging and other demographic changes among people with HIV, and improved screening for and treatment of comorbidities often seen with HIV. This study “aimed to describe the changes in distributions and rates of causes of death over time” in Europeans and North Americans with HIV.
To do this, the investigators traced patterns in causes of death over time in HIV-positive people 16 or older who started antiretroviral therapy (ART) after 1996. They focused on members of 18 ART-CC cohorts in which more than 70% of deaths had an assigned cause. Mortality data came from hospitals or clinician reports, vital statistics agencies, and active follow-up. The research team classified causes of death with input from both a clinician and an algorithm if ICD-9 or ICD-10 codes were available, and otherwise from two clinicians working independently of each other.
The researchers figured time-updated characteristics for six calendar-year periods (1996-1999, 2000-2003, 2004-2007, 2008-2011, 2012-2015, and 2016-2020) and then calculated percentages of deaths attributable to each cause for each period. They used Poisson models to estimate cause-specific mortality rate ratios according to time period, adjusting these models for time-updated age and ART-naive status at the start of each period.
Among the 189,301 people analyzed, 16,832 died to yield a crude mortality rate of 11.1 deaths per 1000 person-years (95% confidence interval 10.9 to 11.3). The proportion of deaths attributable to AIDS dwindled steadily from almost 50% in 1996-1999 to just under 20% in 2016-2020. Rising proportions of deaths due to three other causes offset the drop in AIDS mortality: The proportion of non-AIDS non-hepatitis cancers burgeoned from about 5% in 1996-1999 to about 20% in 2016-2020, and cardiovascular deaths rose from under 10% in 1996-1999 to about 10% in 2016-2020. The proportion of liver deaths also inched up over the decades.


For every 4-year period, cause-specific mortality rate ratios (adjusted for CD4 category, age, and ART-naive status at the start of each period) fell significantly, and most, for AIDS, followed by cardiovascular disease, suicide or accident, liver disease, non-AIDS infection, and non-AIDS nonhepatitis cancer. The adjusted mortality rate ratio for substance use also fell from one 4-year period to the next, but this decline stopped short of statistical significance. Adjusted mortality rate ratios for central nervous system disease and respiratory disease appeared to climb slightly from period to period, but these increases did not reach statistical significance. The overall mortality rate ratio in this study group also fell significantly across 4-year periods.


ART-CC investigators cautioned that they could not assign causes for all deaths. Also, because they combined data from different regions, overall results may blur insights into individual country patterns. Still, the researchers think their findings bolster chances of further cutting mortality in people with HIV via several strategies: (1) targeted cancer screening, (2) preventing cardiovascular disease, (3) preventing infectious diseases through vaccination, (4) preventing pulmonary disease by helping people stop smoking, (5) treating hepatitis, (6) screening for and managing psychiatric disorders, and (7) preventing late HIV diagnoses.
1. Trickey A, McGinnis K, Gill MJ, et al. Causes of death among adults with HIV on ART in Europe and North America: 1996-2019. 30th CROI, Conference on Retroviruses and Opportunistic Infections, February 19-22, 2023, Seattle. Abstract 156.