Requena Maria-Bernarda, Protopopescu Camelia, Stewart Ashleigh C, van Santen Daniela K, Klein Marina B, Jarrin Inmaculada, Berenguer Juan, Wittkop Linda, Salmon Dominique, Rauch Andri, Prins Maria, van der Valk Marc, Sacks-Davis Rachel, Hellard Margaret E, Carrieri Patrizia, Lacombe Karine
Sorbonne Université, INSERM, Pierre Louis Institute of Epidemiology and Public Health, iPLESP, Paris, France.
Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Marseille, France.
Int J Drug Policy. 2024 Feb;124:104311. doi: 10.1016/j.drugpo.2023.104311. Epub 2024 Jan 6.
Among people living with HIV and hepatitis C virus (HCV), people who inject drugs (PWID) have historically experienced higher mortality rates. Direct-acting antivirals (DAA), which have led to a 90 % HCV cure rate independently of HIV co-infection, have improved mortality rates. However, DAA era mortality trends among PWID with HIV/HCV remain unknown. Using data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC), we compared pre/post-DAA availability mortality changes in three groups: PWID, men who have sex with men (MSM), and all other participants.
We included InCHEHC participants with HIV/HCV followed between 2010 and 2019 in Canada, France, the Netherlands, Spain, and Switzerland. All-cause mortality hazard was compared in the three groups, using Cox proportional hazards regression models adjusted for sex, age, advanced fibrosis/cirrhosis, and pre/post DAA availability.
Of the 11,029 participants, 76 % were men, 46 % were PWID, baseline median age was 46 years (interquartile range [IQR] = 40;51), and median CD4 T-cell count was 490 cells/mm (IQR = 327;689). Over the study period (median follow-up = 7.2 years (IQR = 3.7;10.0)), 6143 (56 %) participants received HCV treatment, 4880 (44 %) were cured, and 1322 participants died (mortality rate = 1.81/100 person-years (PY) [95 % confidence interval (CI)=1.72-1.91]). Overall, PWID had higher mortality rates than MSM (2.5/100 PY [95 % CI = 2.3-2.6] vs. 0.8/100 PY [95 % CI = 0.7-0.9], respectively). Unlike women with other transmission modes, those who injected drugs had a higher mortality hazard than men who did not inject drugs and men who were not MSM (adjusted Hazard-Ratio (aHR) [95 % CI] = 1.3[1.0-1.6]). Post-DAA availability, mortality decreased among MSM in the Netherlands, Spain, and Switzerland and increased among PWID in Canada (aHR [95 % CI] = 1.73 [1.15-2.61]).
Post-DAA availability, all-cause mortality did not decrease in PWID. Determinants of cause-specific deaths (drug-related, HIV-related, or HCV-related) need to be identified to explain persistently high mortality among PWID in the DAA era.
在感染艾滋病毒和丙型肝炎病毒（HCV）的人群中，注射吸毒者（PWID）历来死亡率较高。直接抗病毒药物（DAA）已使HCV治愈率达到90%，且与是否合并感染艾滋病毒无关，这改善了死亡率。然而，DAA时代艾滋病毒/丙型肝炎病毒合并感染的注射吸毒者的死亡率趋势仍不明确。利用来自艾滋病毒队列丙型肝炎消除国际协作组（InCHEHC）的数据，我们比较了DAA药物可用前后三组人群的死亡率变化：注射吸毒者、男男性行为者（MSM）和所有其他参与者。
我们纳入了2010年至2019年期间在加拿大、法国、荷兰、西班牙和瑞士接受随访的InCHEHC艾滋病毒/丙型肝炎病毒合并感染参与者。使用Cox比例风险回归模型，对性别、年龄、晚期纤维化/肝硬化以及DAA药物可用前后进行调整，比较三组人群的全因死亡风险。
在11029名参与者中，76%为男性，46%为注射吸毒者，基线中位年龄为46岁（四分位间距[IQR]=40；51），中位CD4 T细胞计数为490个细胞/mm（IQR=327；689）。在研究期间（中位随访时间=7.2年（IQR=3.7；10.0）），6143名（56%）参与者接受了HCV治疗，4880名（44%）治愈，1322名参与者死亡（死亡率=1.81/100人年（PY）[95%置信区间（CI）=1.72 - 1.91]）。总体而言，注射吸毒者的死亡率高于男男性行为者（分别为2.5/100 PY [95% CI=2.3 - 2.6]和0.8/100 PY [95% CI=0.7 - 0.9]）。与其他传播方式的女性不同，注射吸毒的女性比未注射吸毒的男性和非男男性行为者的男性死亡风险更高（调整后风险比（aHR）[95% CI]=1.3[1.0 - 1.6]）。在荷兰、西班牙和瑞士，DAA药物可用后，男男性行为者的死亡率下降，而在加拿大，注射吸毒者的死亡率上升（aHR [95% CI]=1.73 [1.15 - 2.61]）。
DAA药物可用后，注射吸毒者的全因死亡率并未下降。需要确定特定原因死亡（与药物相关、与艾滋病毒相关或与丙型肝炎病毒相关）的决定因素，以解释DAA时代注射吸毒者持续高死亡率的原因。
