Lehman Dara A, Chung Michael H, Mabuka Jennifer M, John-Stewart Grace C, Kiarie James, Kinuthia John, Overbaugh Julie
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
J Acquir Immune Defic Syndr. 2009 Aug 15;51(5):522-9. doi: 10.1097/QAI.0b013e3181aa8a22.
Antiretroviral resistance after short-course regimens used to prevent mother-to-child transmission has consequences for later treatment. Directly comparing the prevalence of resistance after short-course regimens of highly active antiretroviral therapy (HAART) and zidovudine plus single-dose nevirapine (ZDV/sdNVP) will provide critical information when assessing the relative merits of these antiretroviral interventions.
In a clinical trial in Kenya, pregnant women were randomized to receive either ZDV/sdNVP or a short-course of HAART through 6 months of breastfeeding. Plasma samples were collected 3-12 months after treatment cessation, and resistance to reverse transcriptase inhibitors was assessed using both a sequencing assay and highly sensitive allele-specific polymerase chain reaction assays.
No mutations associated with resistance were detectable by sequencing in either the ZDV/sdNVP or HAART arms at 3 months posttreatment, indicating that resistant viruses were not present in >20% of virus. Using allele-specific polymerase chain reaction assays for K103N and Y181C, we detected low levels of resistant virus in 75% of women treated with ZDV/sdNVP and only 18% of women treated with HAART (P = 0.007). Y181C was more prevalent than K103N at 3 months and showed little evidence of decay by 12 months.
Our finding provides evidence that compared with ZDV/sdNVP, HAART reduces but does not eliminate nevirapine resistance.
用于预防母婴传播的短程治疗方案后出现的抗逆转录病毒耐药性会对后续治疗产生影响。在评估这些抗逆转录病毒干预措施的相对优势时，直接比较高效抗逆转录病毒治疗（HAART）短程治疗方案和齐多夫定加单剂量奈韦拉平（ZDV/sdNVP）后耐药性的发生率将提供关键信息。
在肯尼亚的一项临床试验中，孕妇被随机分配接受ZDV/sdNVP或通过6个月母乳喂养的HAART短程治疗。在治疗停止后3 - 12个月收集血浆样本，并使用测序分析和高灵敏度等位基因特异性聚合酶链反应分析评估对逆转录酶抑制剂的耐药性。
在治疗后3个月，通过测序在ZDV/sdNVP组或HAART组中均未检测到与耐药性相关的突变，这表明耐药病毒在超过20%的病毒中不存在。使用针对K103N和Y181C的等位基因特异性聚合酶链反应分析，我们在75%接受ZDV/sdNVP治疗的女性中检测到低水平的耐药病毒，而在接受HAART治疗的女性中仅为18%（P = 0.007）。Y181C在3个月时比K103N更普遍，并且到12个月时几乎没有衰减的迹象。
我们的研究结果提供了证据，表明与ZDV/sdNVP相比，HAART可降低但不能消除奈韦拉平耐药性。
