雷特格韦或依非韦伦对开始抗逆转录病毒治疗的HIV-1/结核病合并感染成人患者细胞相关人类免疫缺陷病毒-1（HIV-1）脱氧核糖核酸及全身炎症的影响
Impact of Raltegravir or Efavirenz on Cell-Associated Human Immunodeficiency Virus-1 (HIV-1) Deoxyribonucleic Acid and Systemic Inflammation in HIV-1/Tuberculosis Coinfected Adults Initiating Antiretroviral Therapy.
作者信息
Delagreverie Héloïse M, Bauduin Claire, De Castro Nathalie, Grinsztejn Beatriz, Chevrier Marc, Jouenne Fanélie, Mourah Samia, Kalidi Issa, Pilotto Jose Henrique, Brites Carlos, Tregnago Barcellos Nemora, Amara Ali, Wittkop Linda, Molina Jean-Michel, Delaugerre Constance
机构信息
Laboratoire de Virologie, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.
INSERM U944, Université de Paris, Paris, France.
出版信息
Open Forum Infect Dis. 2020 Jan 11;7(2):ofz549. doi: 10.1093/ofid/ofz549. eCollection 2020 Feb.
BACKGROUND
In view of the fast viremia decline obtained with integrase inhibitors, we studied the respective effects of initiating efavirenz (EFV) or raltegravir (RAL)-based antiretroviral therapy (ART) regimens on human immunodeficiency virus (HIV)-1 deoxyribonucleic acid (DNA) levels and inflammation biomarkers in the highly inflammatory setting of advanced HIV-1 disease with tuberculosis (TB) coinfection.
METHODS
We followed cell-associated HIV-1 DNA, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), soluble CD14 and D-Dimer levels for 48 weeks after ART initiation in the participants to the ANRS12-180 REFLATE-TB study. This phase II open-label randomized study included ART-naive people with HIV and TB treated with rifampicin to receive RAL 400 mg twice daily (RAL400), RAL 800 mg twice daily (RAL800) or EFV 600 mg QD with tenofovir and lamivudine.
RESULTS
In 146 participants, the median (interquartile range [IQR]) week (W)0 HIV-1 DNA level was 4.7 (IQR, 4.3-5.1) log copies/10 CD4, and the reduction by W48 was -0.8 log copies/10 CD4 on EFV, -0.9 on RAL400, and -1.0 on RAL800 ( = .74). Baseline median (IQR) hsCRP, IL-6, sCD14, and D-Dimer levels were 6.9 (IQR, 3.3-15.6) mg/L, 7.3 (IQR, 3.5-12.3) pg/mL, 3221 (IQR, 2383-4130) ng/mL, and 975 (IQR, 535-1970) ng/mL. All biomarker levels decreased over the study: the overall W0-W48 mean (95% confidence interval) fold-change on ART was 0.37 (IQR, 0.28-0.48) for hsCRP, 0.42 (IQR, 0.35-0.51) for IL-6, 0.51 (IQR, 0.47-0.56) for sCD14, and 0.39 (IQR, 0.32-0.47) for D-Dimers. There were no differences in biomarker reduction across treatment arms.
CONCLUSIONS
In participants with HIV and TB, EFV, RAL400, or RAL800 effectively and equally reduced inflammation and HIV-1 DNA levels.
背景
鉴于整合酶抑制剂能使病毒血症快速下降，我们研究了在合并结核病（TB）的晚期人类免疫缺陷病毒（HIV）-1疾病这种高炎症环境中，启动基于依非韦伦（EFV）或拉替拉韦（RAL）的抗逆转录病毒疗法（ART）方案对HIV-1脱氧核糖核酸（DNA）水平和炎症生物标志物的各自影响。
方法
在ANRS12 - 180 REFLATE - TB研究的参与者中，我们在启动ART后48周跟踪细胞相关HIV-1 DNA、高敏C反应蛋白（hsCRP）、白细胞介素6（IL-6）、可溶性CD14和D-二聚体水平。这项II期开放标签随机研究纳入了未接受过ART的HIV和TB患者，这些患者接受利福平治疗，以每日两次服用400mg RAL（RAL400）、每日两次服用800mg RAL（RAL800）或每日一次服用600mg EFV联合替诺福韦和拉米夫定。
结果
在146名参与者中，第0周（W0）HIV-1 DNA水平的中位数（四分位间距[IQR]）为4.7（IQR，4.3 - 5.1）log拷贝/10 CD4，在第48周时，EFV组下降了 - 0.8 log拷贝/10 CD4，RAL400组下降了 - 0.9，RAL800组下降了 - 1.0（P = 0.74）。基线hsCRP、IL-6、sCD14和D-二聚体水平的中位数（IQR）分别为6.9（IQR，3.3 - 15.6）mg/L、7.3（IQR，3.5 - 12.3）pg/mL、3221（IQR，2383 - 4130）ng/mL和975（IQR，535 - 1970）ng/mL。在研究过程中所有生物标志物水平均下降：ART治疗期间W0 - W48的总体平均（95%置信区间）倍数变化，hsCRP为0.37（IQR，0.28 - 0.48），IL-6为0.42（IQR，0.35 - 0.51），sCD14为0.51（IQR，0.47 - 0.56），D-二聚体为0.39（IQR，0.32 - 0.47）。各治疗组之间生物标志物降低情况无差异。
结论
在HIV和TB患者中，EFV、RAL400或RAL800能有效且同等程度地降低炎症和HIV-1 DNA水平。
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