Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996–99, 2000–03, 2004–07, 2008–11, 2012–15, and 2016–20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996–99 to 16% during 2016–20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4–18·4) during 1996–99 to 7·9 deaths (7·6–8·2) during 2016–20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84–0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79–0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79–0·87), liver-related (0·88, 0·84–0·93), non-AIDS infection-related (0·91, 0·86–0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90–0·97), and suicide or accident-related mortality (0·89, 0·82–0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00–1·14) and decreased slightly in men (0·96, 0·93–0·99).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.

中文翻译：

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1996年至2020年欧洲和北美接受抗逆转录病毒治疗的成人艾滋病毒感染者死亡原因的纵向趋势：队列研究合作

背景

自 1996 年以来，随着有效的抗逆转录病毒疗法 (ART) 的广泛应用，艾滋病毒感染者的死亡率有所下降。随着艾滋病毒感染者年龄的增长，特定原因死亡率的模式也在不断变化。我们的目的是调查欧洲和北美开始接受抗逆转录病毒治疗的艾滋病毒感染者特定原因死亡率的纵向趋势。

方法

在这项协作观察队列研究中，我们使用了 17 个欧洲和北美 HIV 队列的数据，为抗逆转录病毒治疗队列协作提供数据。我们纳入了 1996 年至 2020 年间 16 岁或以上开始接受 ART 的 HIV 感染者的数据。如果国际疾病分类第九版或第十版数据可用，则由临床医生和算法将死亡原因分类为单一原因，或者由两名临床医生独立分类。通过小组讨论解决了分歧。我们使用泊松模型比较了 1996-99、2000-03、2004-07、2008-11、2012-15 和 2016-20 日历期间的特定原因死亡率，并根据时间更新的年龄、CD4 计数、以及该人在每个时期开始时是否未接受过 ART。

发现

在本研究纳入的 189 301 名艾滋病毒感染者中，在 1 519 200 人年的随访期间记录了 16 832 人（8·9%）死亡。13 180 (78·3%) 死亡按原因分类：最常见的原因是艾滋病（4203 例死亡；25·0%）、非艾滋病非肝炎恶性肿瘤（2311 例；13·7%）以及心血管或心脏疾病相关（1403；8·3%）死亡率。死于艾滋病的比例从 1996-99 年的 49% 下降到 2016-20 年的 16%。每1000人年的全因死亡率从1996-99年期间的16·8例死亡（95% CI 15·4–18·4）下降到2016年期间的7·9例死亡（7·6–8·2） 20. 全因死亡率随着时间的推移而下降：每个日历周期的平均调整死亡率为 0·85 (95% CI 0·84–0·86)。特定原因死亡率也有所下降：下降最明显的是艾滋病相关死亡率（0·81；0·79–0·83）。心血管相关（0·83、0·79–0·87）、肝脏相关（0·88、0·84–0·93）、非艾滋病感染相关（0·87）的比率也有所下降。 91, 0·86–0·96)，非艾滋病-非肝细胞癌恶性肿瘤相关死亡率(0·94, 0·90–0·97)，以及自杀或事故相关死亡率(0·89, 0·97) 82–0·95）。通过注射吸毒感染艾滋病毒的女性死亡率上升（1·07、1·00–1·14），男性死亡率略有下降（0·96、0·93–0·99）。

解释

并非所有亚组的大多数主要死因都出现减少，特别是接受抗逆转录病毒治疗的艾滋病毒感染者中与艾滋病相关的死亡。针对高危人群、药物滥用和合并症的干预措施可能会进一步延长艾滋病毒感染者的预期寿命，使其接近普通人群的预期寿命。

资金

美国国家酒精滥用和酒精中毒研究所。