Chi Benjamin H, Sinkala Moses, Mbewe Felistas, Cantrell Ronald A, Kruse Gina, Chintu Namwinga, Aldrovandi Grace M, Stringer Elizabeth M, Kankasa Chipepo, Safrit Jeffrey T, Stringer Jeffrey S A
Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
Lancet. 2007 Nov 17;370(9600):1698-705. doi: 10.1016/S0140-6736(07)61605-5. Epub 2007 Nov 7.
Intrapartum and neonatal single-dose nevirapine are essential components of perinatal HIV prevention in resource-constrained settings, but can induce resistance to other non-nucleoside reverse transcriptase inhibitor drugs. We aimed to investigate whether this complication would be reduced with a single peripartum intervention of tenofovir and emtricitabine.
We randomly assigned 400 HIV-infected pregnant women who sought care at two public-sector primary health facilities in Lusaka, Zambia. One was excluded, 200 were assigned to receive a single oral dose of 300 mg tenofovir disoproxil fumarate with 200 mg emtricitabine under direct observation, and 199 to receive no study drug. Short-course zidovudine and intrapartum nevirapine were offered to all HIV-infected women, according to the local standard of care. Women who met national criteria for antiretroviral therapy were referred for care and not enrolled. Our primary study outcome was resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery. We used standard population sequencing to determine HIV genotypes. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00204308.
Of the 200 women who were randomly assigned to the intervention, 14 were lost to follow-up or withdrew from the study, two did not take study drug according to protocol, and one specimen was lost; 23 of 199 controls were lost to follow-up or withdrew from the study, and three specimens were lost. Women given the intervention were 53% less likely than controls to have a mutation that conferred resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery (20/173 [12%] vs 41/166 [25%]; risk ratio [RR] 0.47, 95% CI 0.29-0.76). We noted postpartum anaemia, the most common serious adverse event in mothers, in four women in each group. 20 of 198 (10%) infants in the intervention group and 23 of 199 (12%) controls had a serious adverse event, mostly due to septicaemia (n=22) or pneumonia (n=8); these events did not differ between groups, and none were judged to be caused by the study intervention.
A single dose of tenofovir and emtricitabine at delivery reduced resistance to non-nucleoside reverse transcriptase inhibitors at 6 weeks after delivery by half; therefore this treatment should be considered as an adjuvant to intrapartum nevirapine.
在资源有限的环境中，分娩时和新生儿单剂量奈韦拉平是围产期预防艾滋病毒的重要组成部分，但可诱导对其他非核苷类逆转录酶抑制剂药物产生耐药性。我们旨在研究在分娩时单次使用替诺福韦和恩曲他滨进行干预是否会减少这种并发症。
我们将在赞比亚卢萨卡的两个公共部门初级卫生设施寻求护理的400名感染艾滋病毒的孕妇随机分组。一名孕妇被排除，200名被分配在直接观察下接受单次口服300mg富马酸替诺福韦二吡呋酯与200mg恩曲他滨，199名不接受研究药物。根据当地护理标准，为所有感染艾滋病毒的妇女提供短程齐多夫定和分娩时奈韦拉平。符合国家抗逆转录病毒治疗标准的妇女被转诊接受护理，未纳入研究。我们的主要研究结局是分娩后6周时对非核苷类逆转录酶抑制剂的耐药性。我们使用标准的群体测序来确定艾滋病毒基因型。分析按方案进行。本研究已在ClinicalTrials.gov注册，编号为NCT00204308。
在随机分配接受干预的200名妇女中，14名失访或退出研究，2名未按方案服用研究药物，1份标本丢失；199名对照组中有23名失访或退出研究，3份标本丢失。接受干预的妇女在分娩后6周时出现对非核苷类逆转录酶抑制剂产生耐药性的突变的可能性比对照组低53%（20/173 [12%] 对41/166 [25%]；风险比 [RR] 0.47，95% CI 0.29 - 0.76）。我们注意到产后贫血是母亲中最常见的严重不良事件，每组各有4名妇女出现。干预组198名婴儿中有20名（10%）和对照组199名中有23名（12%）出现严重不良事件，主要是由于败血症（n = 22）或肺炎（n = 8）；这些事件在两组之间无差异，且均未判定为由研究干预引起。
分娩时单次服用替诺福韦和恩曲他滨可使分娩后6周时对非核苷类逆转录酶抑制剂的耐药性降低一半；因此，这种治疗应被视为分娩时奈韦拉平的辅助治疗。
