Taylor G P, Low-Beer N
Department of Genito-Urinary Medicine and Communicable Diseases, Imperial College School of Medicine, Norfolk Place, London, England.
Drug Saf. 2001;24(9):683-702. doi: 10.2165/00002018-200124090-00004.
Antiretroviral compounds differ from most other new pharmaceutical agents in that they have become widely prescribed in pregnancy in the absence of proof of safety. They are prescribed for the treatment of the mother and to reduce the risk of transmission of HIV to the fetus. In the animal models tested to date, no increased risk of malformations has been demonstrated for some compounds whereas others have been associated with malformations or developmental abnormalities in rats, mice or rabbits and, in the case of efavirenz, monkeys. Zidovudine monotherapy is still prescribed to reduce the risk of mother-to-child transmission of HIV. Combinations of 3 or more compounds are recommended when treatment of the mother is deemed necessary because of advanced HIV infection. Until recently, in vitro toxicity studies relevant to pregnancy were restricted to single agents; no animal teratogenicity or carcinogenesis studies of combination therapy have been published. Despite many thousands of women having taken antiretroviral therapy to reduce the risk of transmission, documented experience in human pregnancy remains sadly lacking, with the possible exception of zidovudine which has been prescribed in clinical trials to several hundred mother-infant pairs. For other compounds and for the numerous permutations of combination therapy, data are available only from small phase I/II studies, from retrospective investigations and from the prospective arm of the Antiretroviral Pregnancy Register (i.e. pregnancies in women taking antiretrovirals who were registered before delivery and then followed up). Antiretroviral monotherapy and combination therapy is widely prescribed in pregnancy because: (i) with appropriate management, which includes antiretroviral therapy, the risk of mother-to-child transmission can be reduced from 15 to 25% to less than 1%; (ii) pregnant women with advanced HIV infection require therapy; (iii) combination therapy with at least 3 compounds significantly reduces morbidity and mortality compared with dual or monotherapy; and (iv) the benefits of therapy for both the mother and the infant outweigh the risk. The choice of antiretroviral therapy in pregnancy may be influenced by the indication (prevention of transmission or maternal treatment), past antiretroviral therapy exposure/drug resistance, effects of pregnancy on the pharmacokinetics of the drug and factors influencing tolerability and adherence. In pregnancy, tolerability may be even more important than usual, especially if therapy exacerbates common complications of pregnancy, such as vomiting and glucose intolerance.
抗逆转录病毒药物与大多数其他新型药物不同，因为在缺乏安全性证据的情况下，它们已在孕期被广泛处方。它们被用于治疗母亲，并降低HIV传播给胎儿的风险。在迄今为止所测试的动物模型中，一些药物并未显示出畸形风险增加，而其他药物则与大鼠、小鼠或兔子的畸形或发育异常有关，依非韦伦还与猴子的畸形或发育异常有关。齐多夫定单药治疗仍被用于降低母婴传播HIV的风险。当由于HIV感染进展而认为有必要治疗母亲时，推荐使用三种或更多药物的联合治疗。直到最近，与孕期相关的体外毒性研究还仅限于单一药物；尚未发表关于联合治疗的动物致畸性或致癌性研究。尽管有成千上万的女性接受了抗逆转录病毒治疗以降低传播风险，但令人遗憾的是，关于人类孕期的记录经验仍然匮乏，可能齐多夫定是个例外，它已在临床试验中被用于几百对母婴。对于其他药物以及联合治疗的众多排列组合，数据仅来自小型I/II期研究、回顾性调查以及抗逆转录病毒妊娠登记处的前瞻性研究（即对在分娩前登记并随后进行随访的服用抗逆转录病毒药物的孕妇的妊娠情况进行研究）。抗逆转录病毒单药治疗和联合治疗在孕期被广泛处方的原因如下：（i）通过适当的管理，包括抗逆转录病毒治疗，母婴传播风险可从15%至25%降低至1%以下；（ii）患有晚期HIV感染的孕妇需要治疗；（iii）与双联或单药治疗相比，至少三种药物的联合治疗可显著降低发病率和死亡率；（iv）治疗对母亲和婴儿的益处超过风险。孕期抗逆转录病毒治疗的选择可能受到治疗指征（预防传播或母亲治疗）、既往抗逆转录病毒治疗暴露/耐药情况、妊娠对药物药代动力学的影响以及影响耐受性和依从性的因素的影响。在孕期，耐受性可能比平时更为重要，尤其是如果治疗会加重孕期常见并发症，如呕吐和葡萄糖不耐受。
