孕妇感染艾滋病毒的治疗:抗逆转录病毒管理方案
Treatment of HIV infection in pregnant women: antiretroviral management options.
作者信息
Loutfy Mona R, Walmsley Sharon L
机构信息
Immune Deficiency Treatment Centre, Montreal General Hospital, McGill University, Montreal, Quebec, Canada.
出版信息
Drugs. 2004;64(5):471-88. doi: 10.2165/00003495-200464050-00002.
Increasing rates of HIV infection in women worldwide, especially among those of childbearing age, reinforce the importance of understanding the management of HIV in pregnancy. Over the past decade, significant advances have been made in the prevention of vertical HIV transmission, including the use of single and combination antiretroviral therapy, elective caesarean section as the preferred mode of delivery and the elimination of breast feeding. Multiple clinical trials assessing antiretroviral therapy in pregnancy have been carried out worldwide. The first pivotal clinical trial, the AIDS Clinical Trials Group (ACTG) 076 study, was conducted in 1994 using a three-part zidovudine regimen. Despite the success of this regimen at decreasing rates of vertical transmission, it is not affordable in many developing countries. Consequently, many international clinical trials have concentrated on short-course antiretroviral regimens including zidovudine alone, zidovudine and lamivudine, and nevirapine alone. In the developed world, the management of nonpregnant HIV-infected individuals has also undergone significant advances and has implications for the management of HIV in pregnancy. A number of countries have participated in the development of guidelines for the management of HIV in pregnancy, which recommend that HIV-infected pregnant women should be offered combination antiretroviral therapy based on viral load and CD4+ cell count cut-offs used for individuals who are not pregnant, preferably with the inclusion of zidovudine. However, to maximise the benefits to their offspring, therapy is recommended at lower viral load thresholds than for nonpregnant adults. For antiretroviral-naive women, therapy is deferred until the second trimester because of the potential and uncertain risk of teratogenesis and the low risk of transmission during this period. Research has also found that maternal factors including viral load, immune status, chorioamnionitis, prematurely ruptured membranes and, to a lesser extent, intravenous drug use and smoking are associated with increased vertical transmission. These represent potentially modifiable risk factors that should be addressed before and throughout pregnancy. Despite the benefits of antiretroviral therapy to reduce HIV vertical transmission, its use can be complicated by known and unknown risks of toxicity to the mother, fetus or both as well as carrying the risk of developing drug-resistant virus. The latter can potentially compromise future treatment options for both the mother and child. Other important challenges include the use of antiretroviral drugs during pregnancy when the mother does not meet criteria for them for her own health, and balancing the relative risks and benefits of elective caesarean section at various degrees of viral load suppression. Clinicians managing HIV in pregnancy need to keep up to date with all the literature to provide optimal care, including counselling to allow mothers to balance the risks and benefits while deciding on treatment for both themselves and their children.
全球范围内女性感染艾滋病毒的比例不断上升,尤其是在育龄女性中,这凸显了了解孕期艾滋病毒管理的重要性。在过去十年中,预防艾滋病毒垂直传播取得了重大进展,包括使用单一和联合抗逆转录病毒疗法、将选择性剖宫产作为首选分娩方式以及杜绝母乳喂养。全球开展了多项评估孕期抗逆转录病毒疗法的临床试验。第一个关键临床试验是艾滋病临床试验组(ACTG)076研究,于1994年进行,采用了三联齐多夫定方案。尽管该方案在降低垂直传播率方面取得了成功,但在许多发展中国家却难以负担。因此,许多国际临床试验集中在短期抗逆转录病毒方案上,包括单独使用齐多夫定、齐多夫定和拉米夫定以及单独使用奈韦拉平。在发达国家,未怀孕的艾滋病毒感染者的管理也取得了重大进展,并对孕期艾滋病毒的管理产生影响。一些国家参与了孕期艾滋病毒管理指南的制定,这些指南建议,应根据未怀孕个体使用的病毒载量和CD4+细胞计数临界值,为感染艾滋病毒的孕妇提供联合抗逆转录病毒疗法,最好包含齐多夫定。然而,为了使对其后代的益处最大化,建议在低于未怀孕成年人的病毒载量阈值时进行治疗。对于未接受过抗逆转录病毒治疗的女性,由于存在潜在且不确定的致畸风险以及在此期间传播风险较低,治疗推迟至孕中期。研究还发现,包括病毒载量、免疫状态、绒毛膜羊膜炎、胎膜早破以及在较小程度上的静脉吸毒和吸烟等母体因素与垂直传播增加有关。这些是潜在的可改变风险因素,在孕前和孕期都应加以应对。尽管抗逆转录病毒疗法有助于减少艾滋病毒垂直传播,但它可能因对母亲、胎儿或两者已知和未知的毒性风险以及产生耐药病毒的风险而变得复杂。后者可能会损害母亲和孩子未来的治疗选择。其他重要挑战包括在母亲自身健康不符合用药标准时在孕期使用抗逆转录病毒药物,以及在不同程度的病毒载量抑制情况下权衡选择性剖宫产的相对风险和益处。管理孕期艾滋病毒的临床医生需要跟上所有文献的最新进展,以提供最佳护理,包括提供咨询,以便母亲在决定自身和孩子的治疗时能够权衡风险和益处。