Simoncini Gina, Li Jun, Mayer Cynthia, Collins Lauren F, Battalora Linda, Buchacz Kate
AbsoluteCare, Philadelphia, Pennsylvania, USA.
Division of HIV Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
AIDS Res Hum Retroviruses. 2025 Aug;41(8):400-410. doi: 10.1089/aid.2025.0001. Epub 2025 May 21.
Persons with HIV (PWH) have disproportionate hepatitis C virus (HCV) infection prevalence and liver-related morbidity and mortality. These sequelae may be alleviated by curative direct-acting antiviral (DAA) treatment; however, longitudinal effects of DAAs on clinical biomarkers are not well-characterized. We included PWH enrolled in the HIV Outpatient Study (HOPS) who were prescribed DAAs and DAA-naïve PWH of comparable age, sex, race/ethnicity, and fibrosis-4 (FIB-4) profiles. We contrasted the DAA effect on longitudinal trajectories of immunological and hepatic markers using generalized linear mixed models (GLMM) from 2010 to 2020. Of 347 PWH/HCV coinfection, median age was 53.8 years, 30.5% were women, 67.1% were publicly insured, 44.4% were non-Hispanic Black, and 153 (44.1%) were prescribed DAAs (median follow-up = 3.55 years). In multivariable GLMM analysis, DAA treatment was associated with [mean (95% confidence interval)] faster decline in alanine aminotransferase of -7.86 mu/µL/year (-15.39, -0.33) and faster increase in platelets of 6.99 mu/µL/year (2.89, 11.09). Changes in aspartate aminotransferase were comparable between groups. FIB-4 decreased in the DAA-treated but not the DAA-naïve group: -0.26 (-0.41, -0.11) versus 0.02 (-0.16, 0.20)/year, respectively. There was a faster increase in cluster of differentiation (CD)4 count of 0.05 (0.03-0.08) and CD8 count of 0.04 (0.02-0.07) log cells/mL/year in the DAA-treated compared with the DAA-naïve group ( < .001), but not in the CD4/CD8 ratio ( = .36). Among U.S. PWH/HCV coinfection treated with DAAs, we found modest changes in immunological markers and substantial improvements in hepatic markers modeled over 4 years of DAA treatment. Curative DAA treatment is critical to mitigate advanced liver fibrosis.
感染人类免疫缺陷病毒（HIV）的人群（PWH）丙型肝炎病毒（HCV）感染率、肝脏相关发病率和死亡率均过高。这些后遗症可通过根治性直接抗病毒（DAA）治疗得到缓解；然而，DAA对临床生物标志物的长期影响尚未得到充分描述。我们纳入了参加HIV门诊研究（HOPS）并接受DAA治疗的PWH，以及年龄、性别、种族/民族和纤维化-4（FIB-4）特征相当但未接受DAA治疗的PWH。我们使用广义线性混合模型（GLMM）对比了2010年至2020年DAA对免疫和肝脏标志物纵向轨迹的影响。在347例PWH/HCV合并感染患者中，中位年龄为53.8岁，30.5%为女性，67.1%有公共保险，44.4%为非西班牙裔黑人，153例（44.1%）接受了DAA治疗（中位随访时间=3.55年）。在多变量GLMM分析中，DAA治疗与[平均值（95%置信区间）]丙氨酸转氨酶每年更快下降-7.86 μ/µL（-15.39，-0.33）以及血小板每年更快增加6.99 μ/µL（（2.89，11.09）相关。两组间天冬氨酸转氨酶的变化相当。FIB-4在接受DAA治疗的组中下降，而在未接受DAA治疗的组中未下降：分别为-0.26（-0.41，-0.11）/年和0.02（-0.16，0.20）/年。与未接受DAA治疗的组相比，接受DAA治疗的组中分化簇（CD）4细胞计数每年更快增加0.05（0.03 - 0.08）log细胞/mL，CD8细胞计数每年更快增加0.04（0.02 - 0.07）log细胞/mL（P <.001），但CD4/CD8比值无变化（P =.36）。在美国接受DAA治疗的PWH/HCV合并感染患者中，我们发现在4年DAA治疗过程中，免疫标志物有适度变化，肝脏标志物有显著改善。根治性DAA治疗对于减轻晚期肝纤维化至关重要。
