与替诺福韦酯相比，丙酚替诺福韦的精液替诺福韦浓度、病毒抑制及精液质量（西班牙HIV/AIDS研究网络，PreEC/RIS 40）
Seminal Tenofovir Concentrations, Viral Suppression, and Semen Quality With Tenofovir Alafenamide, Compared With Tenofovir Disoproxil Fumarate (Spanish HIV/AIDS Research Network, PreEC/RIS 40).
作者信息
Imaz Arkaitz, Niubó Jordi, Cottrell Mackenzie L, Perez Emilia, Kashuba Angela D M, Tiraboschi Juan M, Morenilla Sandra, Garcia Benito, Podzamczer Daniel
机构信息
Human Immunodeficiency Virus and Sexually Transmitted Infections Unit, Department of Infectious Diseases.
Department of Microbiology, Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Spain.
出版信息
Clin Infect Dis. 2019 Sep 27;69(8):1403-1409. doi: 10.1093/cid/ciy1074.
BACKGROUND
This study assessed the penetration and efficacy of tenofovir alafenamide (TAF) in the male genital tract (MGT) and the semen quality of individuals infected with human immunodeficiency virus (HIV)-1 who were treated with a TAF-containing regimen.
METHODS
This was a prospective, open-label, single-arm study of 14 virologically-suppressed, HIV-1-infected men on stable antiretroviral therapy with elvitegravir, cobicistat, emtricitabine (E/C/F) and tenofovir disoproxil fumarate (TDF) who switched to E/C/F and TAF. At baseline (pre-switch) and at 12 weeks post-switch, we measured HIV-1 RNA in seminal plasma (SP) and blood plasma (BP), tenofovir (TFV) in SP and BP, and TFV-diphosphate (dp) in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs) at the end of the dosing interval (C24h). Semen quality was assessed before switching and after 12 weeks on TAF.
RESULTS
With TAF, TFV C24 was 11.9-fold higher in SP than in BP. This concentration was significantly lower than TFV C24 in SP with TDF, but 9.6-fold higher than the 50% inhibitory concentration (IC50) (11.5 ng/mL). By contrast, the median TFV-dp concentration achieved with TAF in SMCs was 6% that of TFV-dp in PBMCs. The TFV-dp SMC:PBMC ratio was also significantly lower with TAF. Nonetheless, TFV-dp C24 in SMC was comparable with TAF and TDF. All the patients had HIV-1 RNA <40 copies/mL in BP and SP at baseline and at 12 weeks post-switch. No significant differences were observed in semen quality between TAF and TDF.
CONCLUSIONS
Extracellular and intracellular seminal TFV distribution differs between TAF and TDF. Nevertheless, both formulations, combined with elvitegravir/cobicistat/emtricitabine, maintained HIV-1 RNA suppression in semen. Differences in MGT distribution were not associated with differences in semen quality.
CLINICAL TRIALS REGISTRATION
EudraCT: 2016-001371-69.
背景
本研究评估了替诺福韦艾拉酚胺（TAF）在男性生殖道（MGT）中的渗透情况及疗效，以及接受含TAF方案治疗的人类免疫缺陷病毒（HIV）-1感染者的精液质量。
方法
这是一项前瞻性、开放标签、单臂研究，纳入了14名病毒学抑制的HIV-1感染者，他们接受基于埃替拉韦、考比司他、恩曲他滨（E/C/F）和替诺福韦酯（TDF）的稳定抗逆转录病毒治疗，后改为E/C/F和TAF治疗。在基线（换药前）和换药后12周，我们测量了精液血浆（SP）和血液血浆（BP）中的HIV-1 RNA、SP和BP中的替诺福韦（TFV），以及给药间隔结束时（C24h）外周血单核细胞（PBMCs）和精液单核细胞（SMCs）中的替诺福韦二磷酸（dp）。在换药前和TAF治疗12周后评估精液质量。
结果
使用TAF时，SP中的TFV C24比BP中的高11.9倍。该浓度显著低于使用TDF时SP中的TFV C24，但比50%抑制浓度（IC50）（11.5 ng/mL）高9.6倍。相比之下，TAF在SMCs中达到的TFV-dp中位数浓度是PBMCs中TFV-dp浓度的6%。TAF的TFV-dp SMC:PBMC比值也显著更低。尽管如此，SMCs中的TFV-dp C24在TAF和TDF之间相当。所有患者在基线和换药后12周时，BP和SP中的HIV-1 RNA均<40拷贝/mL。TAF和TDF之间的精液质量未观察到显著差异。
结论
TAF和TDF在精液中细胞外和细胞内TFV的分布不同。然而，两种制剂与埃替拉韦/考比司他/恩曲他滨联合使用时，均可维持精液中HIV-1 RNA的抑制。MGT分布的差异与精液质量的差异无关。
临床试验注册
EudraCT：2016-001371-69。
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