Nolan David, Mallal Simon
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia.
J HIV Ther. 2003 Feb;8(1):2-6.
The use of alternative nucleoside reverse transcriptase inhibitors (NRTIs) to the thymidine analogues stavudine (d4T) and zidovudine(ZDV) has been advocated as a means of limiting long-term NRTI-associated toxicity, particularly the development of lipoatrophy or fat wasting. This approach reflects an increasing knowledge of the distinct toxicity profiles of NRTI drugs. However, recent clinical trials have demonstrated that the use of thymidine analogue NRTIs and newer alternative backbone NRTIs, such as tenofovir (TNF) and abacavir (ABC), is associated with comparable short-term efficacy and tolerability. Given the importance of toxicity profile differences in determining clinical management, it is important to recognise that d4T and ZDV cary significantly different risks for long-term NRTI toxicity. Recognising that all NRTIs, including thymidine analogues, have individual toxicity profiles provides a more appropriate basis for selecting optimal antiretroviral therapy. The safety and efficacy of TNF and ABC are also reviewed here, although the available data provide only limited knowledge of the long-term effects of these drugs in terms of toxicity and antiviral durability.
有人主张使用胸苷类似物司他夫定（d4T）和齐多夫定（ZDV）以外的替代核苷类逆转录酶抑制剂（NRTIs），作为限制长期使用NRTIs相关毒性的一种手段，尤其是脂肪萎缩或脂肪消耗的发生。这种方法反映了对NRTI药物不同毒性特征的认识不断增加。然而，最近的临床试验表明，使用胸苷类似物NRTIs和较新的替代主干NRTIs，如替诺福韦（TNF）和阿巴卡韦（ABC），具有相当的短期疗效和耐受性。鉴于毒性特征差异在确定临床管理中的重要性，重要的是要认识到d4T和ZDV对长期NRTI毒性具有显著不同的风险。认识到所有NRTIs，包括胸苷类似物，都有各自的毒性特征，为选择最佳抗逆转录病毒疗法提供了更合适的基础。本文还对TNF和ABC的安全性和疗效进行了综述，尽管现有数据仅提供了关于这些药物在毒性和抗病毒持久性方面长期影响的有限知识。
