Big falls in HIV deaths in high-income countries – except for injecting drug users

While there have been reductions in the rates of most major causes of death among people with HIV in North America and Europe since 1996, people who inject drugs – particularly women – remain vulnerable to early death.

Background

Before 1996 – when combination antiretroviral therapy (ART) became the mainstay of HIV treatment – death from AIDS was a near inevitability, even in high-income countries. Due to ART’s high effectiveness at suppressing HIV, AIDS-related deaths have declined steeply, particularly in Europe and North America.

However, between 1996 and 2012, ART was usually only started when a person’s CD4 count fell below a certain level or based on symptoms. This changed globally based on conclusive findings from the INSIGHT START and TEMPRANO studies – these indicated that immediate ART initiation leads to the best outcomes, regardless of CD4 count and disease stage. Thus, test and treat approaches that aim to minimise the time between diagnosis and starting treatment were implemented globally between 2012 and 2015.

People living with HIV on effective treatment are now more likely to die at an older age from age-related illnesses, such as heart disease or cancer than AIDS. Additionally, death from substance use and hepatitis C remains higher among people living with HIV.

The study

Researchers used data from 17 European and North American HIV cohorts that form part of the Antiretroviral Therapy Cohort Collaboration. This included data from 189,301 people living with HIV aged 16 and older who had started ART between 1996 and 2020. Six different periods were considered: 1996 to 1999, 2000 to 2003, 2004 to 2007, 2008 to 2011, 2012 to 2015 and 2016 to 2020. This resulted in over 1.5 million person-years of follow-up time.

Cause of death was classified by a clinician and an algorithm (based on the International Classification of Diseases) or by two clinicians.

The average age of cohort members increased over time. Of the participants who were alive during each period, 55% were between the ages of 40 to 59 between 2016 and 2020, whereas 68% were aged 16 to 39 between 1996 and 1999. Gay and bisexual men made up the single largest category of people living with HIV based on mode of transmission across time periods, at 43% in the last period, up from 35% during the first period. Most people had a CD4 count of 500 or more during the period 2016 to 2020 (58%), compared to only 15% between 1996 and 1999. For the final period, White people made up 58% (compared to 77% between 1996 and 1999), while Black people made up 19% (compared to 11% between 1996 to 1999) of the sample.

Findings

Between 1996 and 2020, 25% of 16,832 deaths in the sample were caused by AIDS. Non-AIDS and non-hepatitis related cancers caused 14%, while 8% were caused by heart disease. Over this period, the proportion of AIDS-related deaths declined by 33%. Similarly, death rates from any cause declined from a high of 17.1 per 1,000 between 2000 and 2003 to 7.9 per 1000 between 2016 to 2020, indicating the lengthened lifespan of people living with HIV. Between 1996 and 1999, half of those who died were under 39 years of age, whereas two decades later, half of those who died were under 56. Consistent with the fact the people with HIV are living longer, the proportion of deaths due to cancers increased by 14% over this period.

When looking at the mortality rate ratio, a comparative measure (the 2000 to 2003 period was chosen as the comparison period), and controlling for factors such as CD4 count and when the person started ART, the researchers found that the average all-cause mortality rate ratio decreased by 15% by 2020 (adjusted Mortality Rate Ratio = 0.85, 95% Confidence Interval: 0.84-0.86). Rates of most causes of death declined; this was seen for AIDS-related deaths, those related to heart and liver disease, other cancers, and suicide or accident-related deaths. However, rate ratio declines were not seen for deaths related to central nervous system conditions (such as Alzheimer’s and Parkinson’s), respiratory illnesses and substance use.

Rates of death from all causes declined over time for gay and bisexual men and for both straight men and women. Declines in death rates due to heart-related illness were most marked among gay and bisexual men. However, death rates among women who acquired HIV through injecting drug use increased by 7% (aMRR = 1.07, 95% CI: 1.00-1.14) and decreased only slightly among men who inject drugs (aMRR = 0.96, 95% CI = 0.93-0.99). Rates of substance use-related death declined on average among people with HIV in Europe, but not in North America, possibly due to the opioid crisis there – opioid related deaths are ten times higher in North America than in Europe.

Conclusion

“Progress in reducing cause-specific mortality has not been evenly spread across subgroups of people with HIV, often with the most marginalised populations experiencing the least benefits,” the authors concluded.

“Men who acquired HIV through injecting drug use had the lowest reductions in mortality, while there was some evidence of increases in mortality among women who acquired HIV through injecting drug use. People with histories of substance use conditions have higher rates of homelessness and other comorbidities and often experience additional barriers and stigma while attempting to access care. This indicates that targeted interventions, such as addressing social determinants of health and bringing comorbidity care to needle and syringe dispensing locations, are required for people who acquired HIV through injecting drug use.”