抗逆转录病毒初治的 HIV-1 感染者中，比克替拉韦/恩曲他滨/替诺福韦艾拉酚胺治疗对人类免疫缺陷病毒（HIV）RNA 衰减动力学和比克替拉韦在生殖道和直肠中的分布：西班牙艾滋病毒/艾滋病研究网络（HIV/AIDS Research Network，PreEC/RIS 58）研究
Dynamics of the Decay of Human Immunodeficiency Virus (HIV) RNA and Distribution of Bictegravir in the Genital Tract and Rectum in Antiretroviral-naive Adults Living With HIV-1 Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (Spanish HIV/AIDS Research Network, PreEC/RIS 58).
机构信息
Human Immunodeficiency Virus (HIV) and Sexually Transmitted Infection (STI) Unit, Department of Infectious Diseases, Bellvitge University Hospital, Bellvitge Biomedical Research Institute, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
Department of Microbiology, Bellvitge University Hospital, Bellvitge Biomedical Research Institute, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
出版信息
Clin Infect Dis. 2021 Oct 5;73(7):e1991-e1999. doi: 10.1093/cid/ciaa1416.
BACKGROUND
The pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)-1 RNA in genital fluids and the rectum have not yet been addressed.
METHODS
We conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay.
RESULTS
The study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41-3.79), 4.19 (2.98-4.70), and 2.56 (1.61-3.56) log10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1-923) ng/mL, 74.1 (6.0-478.5) ng/g, and 61.6 (14.4-1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively.
CONCLUSIONS
BIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL).
CLINICAL TRIALS REGISTRATION
EudraCT 2018-002310-12.
背景
比克替拉韦（BIC）的药代动力学及其与生殖器液和直肠中人类免疫缺陷病毒（HIV）-1 RNA 衰减的关系尚未得到解决。
方法
我们对 15 名男性和 8 名女性艾滋病毒-1 初治患者进行了前瞻性、多中心研究，这些患者正在接受 BIC/恩曲他滨（FTC）/替诺福韦艾拉酚胺（TAF）治疗。在基线、第 3、7、14 和 28 天以及第 12 和 24 周时，测量血液血浆（BP）、精液浆（SP）、直肠液（RF）和宫颈阴道液（CVF）中的 HIV-1 RNA（定量下限为 40 拷贝/mL）。第 28 天和第 12 周时，使用经过验证的液相色谱-串联质谱分析方法，定量测定 BP、SP、CVF 和直肠组织（RT）中 24 小时后（C24h）的总游离 BIC 和蛋白结合 BIC 浓度。
结果
研究人群包括 15 名男性和 8 名女性。在 SP、RF 和 CVF 中，基线时 HIV-1 RNA>40 拷贝/mL 的分别有 12/15、13/15 和 4/8 名个体，中位数分别为 3.54（2.41-3.79）、4.19（2.98-4.70）和 2.56（1.61-3.56）log10 拷贝/mL。SP 中的初始衰减斜率明显低于 RF 和 BP。SP 和 RF 中的 HIV-1 RNA 达到不可检测水平的时间明显短于 BP。所有女性在第 14 天 CVF 中均达到 HIV-1 RNA 不可检测水平。SP、RT 和 CVF 中的总游离 BIC 浓度中位数分别为 65.5（20.1-923）ng/mL、74.1（6.0-478.5）ng/g 和 61.6（14.4-1760.2）ng/mL，分别为 BP 浓度的 2.7%、2.6%和 2.8%，游离蛋白部分分别为 51.1%、44.6%和 42.6%。
结论
BIC/FTC/TAF 导致生殖器液和直肠液中的 HIV-1 RNA 快速衰减。SP、RT 和 CVF 中的游离 BIC 浓度远远超过了半最大有效浓度（EC50）值（1.1ng/mL）。
临床试验注册
EudraCT 2018-002310-12。
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