HIV-1 感染孕妇接受有限疗程抗逆转录病毒治疗后发生的产后抗逆转录病毒耐药性。
Postpartum antiretroviral drug resistance in HIV-1-infected women receiving pregnancy-limited antiretroviral therapy.
机构信息
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
AIDS. 2010 Jan 2;24(1):45-53. doi: 10.1097/QAD.0b013e32832e5303.
BACKGROUND
Pregnancy-limited antiretroviral therapy (PLAT) drastically reduces HIV-1 transmission to the newborn, but may select for antiretroviral drug resistance mutations in mothers.
METHODS
We evaluated antiretroviral-naive, HIV-1-infected pregnant women who received PLAT between 1998 and 2005, and had 2-month or 6-month postpartum plasma samples available with HIV-1 RNA levels more than 500 copies/ml. Postpartum drug resistance mutation rates were assessed blindly using population sequencing and allele-specific PCR (ASPCR) of the M184V, K103N and D30N mutations. Factors associated with selection of drug resistance mutations were investigated.
RESULTS
One hundred and forty-six women were included. All women received zidovudine and lamivudine during pregnancy; 76% also received nelfinavir and 8.2% nevirapine. Resistance data were available from 114 women (78%). Postpartum rates of single-class, dual-class, and triple-class resistance were, respectively, 43, 6.1 and 0% (63.2, 10.5 and 1.7% by ASPCR). In women receiving dual or triple PLAT, respectively, postpartum M184V/I rates were 65% (95% by ASPCR) and 28.7% (51.6% by ASPCR), respectively (P < 0.01). Postpartum nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance rates among women receiving nevirapine were 25% for K103N (37.5% by ASPCR) and 12.5% for Y188C. Protease inhibitor resistance rates in women receiving nelfinavir were 1.1% for D30N (1.1% by ASPCR) and 1.1% for L90M. Dual versus triple PLAT and prolonged zidovudine exposure were associated with selection of M184V. Nevirapine use and length of zidovudine and lamivudine exposure were associated with selection of K103N.
CONCLUSION
PLAT is associated with frequent selection of resistance to drugs with low-genetic barrier. Triple-drug PLAT decreases the odds for M184V selection. Routine postpartum genotypic resistance testing may be useful to guide future treatment decisions in mothers.
背景
妊娠限制抗逆转录病毒疗法（PLAT）可显著降低 HIV-1 向新生儿的传播，但可能会在母亲中选择出抗逆转录病毒药物耐药突变。
方法
我们评估了 1998 年至 2005 年间接受 PLAT 的抗逆转录病毒初治、HIV-1 感染的孕妇，并在产后 2 个月或 6 个月获得了 HIV-1 RNA 水平超过 500 拷贝/ml 的血浆样本。使用人群测序和 M184V、K103N 和 D30N 突变的等位基因特异性 PCR（ASPCR）对产后耐药突变率进行盲法评估。研究了与耐药突变选择相关的因素。
结果
共纳入 146 名女性。所有女性在妊娠期间均接受齐多夫定和拉米夫定治疗；76%的女性还接受奈韦拉平治疗，8.2%的女性接受依法韦仑治疗。114 名女性（78%）获得了耐药数据。单药、双药和三药耐药的产后发生率分别为 43%、6.1%和 0%（ASPCR 分别为 63.2%、10.5%和 1.7%）。分别接受双药和三药 PLAT 的女性产后 M184V/I 发生率分别为 65%（ASPCR 为 95%）和 28.7%（ASPCR 为 51.6%）（P<0.01）。接受奈韦拉平治疗的女性中，非核苷类逆转录酶抑制剂（NNRTI）耐药率分别为 K103N 25%（ASPCR 为 37.5%）和 Y188C 12.5%。接受奈韦拉平治疗的女性中蛋白酶抑制剂耐药率分别为 D30N 1.1%（ASPCR 为 1.1%）和 L90M 1.1%。与三药 PLAT 相比，双药 PLAT 和延长齐多夫定暴露与 M184V 的选择有关。奈韦拉平的使用以及齐多夫定和拉米夫定的暴露时间与 K103N 的选择有关。
结论
PLAT 与耐药性选择相关，耐药性对具有低遗传屏障的药物的选择频率较高。三药 PLAT 可降低 M184V 选择的几率。产后常规基因型耐药性检测可能有助于指导母亲未来的治疗决策。
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