Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand.
Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand.
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DOI：
10.1097/qad.0000000000000865
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发表时间：
2015-11-28
期刊：
影响因子：
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通讯作者：
PHPT-5 study investigators
中科院分区：
文献类型：
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作者：
Lallemant M;Le Coeur S;Sirirungsi W;Cressey TR;Ngo-Giang-Huong N;Traisathit P;Klinbuayaem V;Sabsanong P;Kanjanavikai P;Jourdain G;Mcintosh K;Koetsawang S;PHPT-5 study investigators
围产期单剂量奈韦拉平 (sdNVP) 选择耐药突变。该试验的目的是比较两种母亲 sdNVP 保留方案与标准齐多夫定 (ZDV)/sdNVP 预防。 PHPT-5 是在泰国进行的一项随机、部分双盲、安慰剂对照、非劣效性试验 (NCT00409591)。受试者是 CD4 ≥250 个细胞/mm3 的女性及其婴儿。所有妇女从妊娠 28 周起及其新生儿开始接受为期一周的 ZDV。妇女还被随机分配接受 A) NVP-NVP（参考）：产妇产时 sdNVP，带有 ZDV+拉米夫定 7 天“尾巴”，加上婴儿 NVP（立即一剂，48 小时后另一剂）； B) 仅婴儿 NVP：sdNVP 和“尾巴”的母体安慰剂，加上婴儿 NVP； C) LPV/r：从 28 周开始的母体 LPV/r。婴儿是配方奶喂养的。 HIV 诊断通过 DNA-PCR 确定。 2009 年 1 月至 2010 年 9 月期间，435 名女性被随机分组。泰国指南发生变化，建议所有孕妇接受抗逆转录病毒联合治疗，因此提前终止了应计项目。分析了 405 名母亲和 407 名活产婴儿的数据。各组之间的基线特征相似。 NVP-NVP 组的意向治疗传播率为 3.8%（95% CI：1.2-8.6），纯婴儿 NVP 组为 1.6%（0.2-5.6），LPV/r 组为 1.4%（0.4-5.1）。治疗后的发生率分别为 2.2% (0.5–6.4)、3.2% (0.9–7.9) 和 1.5% (0.2–5.2)。与传播独立相关的因素是预防持续时间<8周（aOR 15.5；3.6-66.1）和基线病毒载量≥4 log10拷贝/mL（aOR 10.9；1.3-91.5）。治疗方案似乎很安全。所有臂的传播率均较低，但未证明非劣效性。分娩前至少 8 周的抗逆转录病毒预防对于最大程度地降低传播风险是必要的。
Perinatal single-dose nevirapine (sdNVP) selects for resistance mutations. The objective of this trial was to compare two maternal sdNVP-sparing regimens with standard zidovudine (ZDV)/sdNVP prophylaxis. PHPT-5 was a randomized, partially double-blind placebo-controlled, non-inferiority trial in Thailand (NCT00409591). Subjects were women with CD4 ≥250 cells/mm3 and their infants. All women received ZDV from 28 weeks’ gestation and their newborn infants for one week. Women were also randomized to receive A) NVP-NVP (reference): maternal intrapartum sdNVP with a 7-day “tail” of ZDV+lamivudine, plus infant NVP (one dose immediately, another 48 hours later); B) Infant-only NVP: maternal placebos for sdNVP and the “tail”, plus infant NVP; C) LPV/r: maternal LPV/r starting at 28 weeks. Infants were formula-fed. HIV-diagnosis was determined by DNA-PCR. 435 women were randomized between January 2009 and September 2010. Accrual was terminated prematurely following a change in Thai guidelines recommending antiretroviral combination therapy for all pregnant women. Data on 405 mothers and 407 live-born children were analyzed. Baseline characteristics were similar between arms. Intent-to-treat transmission rates were 3.8% (95% CI: 1.2–8.6) in NVP-NVP, 1.6% (0.2–5.6) in infant-only NVP and 1.4% (0.4–5.1) in LPV/r arms. As-treated rates were 2.2% (0.5–6.4), 3.2% (0.9–7.9) and 1.5% (0.2–5.2), respectively. Factors independently associated with transmission were prophylaxis duration <8 weeks (aOR 15.5; 3.6–66.1) and viral load at baseline ≥4 log10 copies/mL (aOR 10.9; 1.3–91.5). Regimens appeared safe. Transmission rates in all arms were low but non-inferiority was not proven. Antiretroviral prophylaxis for ≥8 weeks before delivery is necessary to minimize transmission risk.