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替诺福韦联合去羟肌苷作为HIV感染者的核苷类逆转录酶抑制剂主干治疗方案。

Tenofovir plus didanosine as Nrti backbone in HIV-infected subjects.

作者信息

Bongiovanni Marco, Tordato Federica

机构信息

Clinic of Infectious Diseases, S.Paolo Hospital, University of Milan, Via di Rudinì 8, 20142 Milan, Italy.

出版信息

Curr Med Chem. 2006;13(23):2789-93. doi: 10.2174/092986706778521931.

Abstract

Nucleoside reverse transcriptase inhibitors (NRTI) are essential components of highly active antiretroviral treatment (HAART). Although several combinations can be used as NRTI backbones, not all are associated with good virological and/or immunological results. In particular, some NRTI combinations should be avoided due to antagonism (zidovudine plus stavudine) or to high rate of toxicity (didanosine plus stavudine). Tenofovir (TDF) and didanosine (ddI) are among the more often prescribed NRTI for their convenient posology (one pill each per day), relatively high genetic barrier for resistance, quite acceptable safety profile and remarkable antiviral potency when such drugs have been used as single drug or in combinations with other NRTIs. However, antiretroviral regimens containing TDF and ddI have been associated with a high rate of virological failure in HIV-infected naïve patients due to possible drug-interactions. The virological efficacy of this backbone in HIV-infected, HAART pre-treated subjects, is still controversial. Aim of this review is to assess the possible role that antiretroviral regimens containing TDF and ddI can have in the treatment of HIV-positive subjects, focusing on their plasmatic and/or intracellular interactions to optimize the antiretroviral efficacy and minimize the toxicities of this combination.

摘要

核苷类逆转录酶抑制剂(NRTI)是高效抗逆转录病毒治疗(HAART)的重要组成部分。尽管有几种组合可用作NRTI主干,但并非所有组合都能带来良好的病毒学和/或免疫学效果。特别是,由于拮抗作用(齐多夫定加司他夫定)或高毒性发生率(去羟肌苷加司他夫定),应避免使用某些NRTI组合。替诺福韦(TDF)和去羟肌苷(ddI)是较常处方的NRTI,因为它们给药方便(每天各一片),耐药的遗传屏障相对较高,安全性相当可接受,并且当这些药物作为单一药物或与其他NRTI联合使用时具有显著的抗病毒效力。然而,由于可能存在药物相互作用,含TDF和ddI的抗逆转录病毒方案在初治HIV感染患者中与高病毒学失败率相关。这种主干方案在接受过HAART治疗的HIV感染受试者中的病毒学疗效仍存在争议。本综述的目的是评估含TDF和ddI的抗逆转录病毒方案在治疗HIV阳性受试者中可能发挥的作用,重点关注它们在血浆和/或细胞内的相互作用,以优化抗逆转录病毒疗效并将该组合的毒性降至最低。

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