Prevention of Mother-to-Child Transmission of HIV-1 Through Breastfeeding by Treating Mothers With Triple Antiretroviral Therapy in Dar es Salaam, Tanzania: The Mitra Plus Study
Prevention of Mother-to-Child Transmission of HIV-1 Through Breastfeeding by Treating Mothers With Triple Antiretroviral Therapy in Dar es Salaam, Tanzania: The Mitra Plus Study
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DOI：
10.1097/qai.0b013e3181b323ff
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发表时间：
2009-11-01
影响因子：
3.6
通讯作者：
Biberfeld, Gunnel
中科院分区：
文献类型：
--
作者：
Kilewo, Charles;Karlsson, Katarina;Biberfeld, Gunnel
目的：本研究的主要目的是通过在母乳喂养期间使用高效抗逆转录病毒疗法 (HAART) 治疗 HIV-1 感染妇女，从而减少 HIV-1 的母乳传播。方法：Mina。 Plus 是一项开放标签、非随机、前瞻性队列研究，达累斯萨拉姆感染 HIV-1 的孕妇接受齐多夫定 (ZDV) + 拉米夫定 (3TC) + 奈韦拉平 (NVP) 治疗。对于 CD4 细胞计数 > 200 个细胞/微升或对 NVP 产生不良反应的母亲，NVP 随后被奈非那韦取代。 HAART 于妊娠 34 周开始。对于有症状的 HIV 感染或 CD4 细胞计数低于 200 个/微升的女性，如果可能，应尽早开始 HAART。除那些因自身健康原因需要HAART的母亲外，母亲的治疗在6个月时停止。婴儿出生后接受 ZDV + 3TC 1 周。建议母亲纯母乳喂养，并在 5 至 6 个月大时突然断奶。使用 Kaplan-Meier 生存技术分析 HIV-1 的传播。使用 Cox 回归与 Petra 试验组 A 的母乳喂养人群进行比较。结果：HIV-1 传播分析中纳入了 441 名婴儿。产后 6 周时 HIV-1 的累积传播率为 4.1% [95% 置信区间 (CI)：2.2 至 6.0]，6 个月时为 5.0%（95% CI：2.9 至 7.1），18 个月时为 6.0%（95% CI：3.7 至 8.3）。 6周至6个月期间HIV传播的累积风险为1.0%，6个月至18个月期间为1.1%。产后 6 个月时的累积 HIV 感染率或死亡率为 8.6%（95% CI：6.0 至 11.2），18 个月时为 13.6%（95% CI：10.3 至 16.9）。入组时的病毒载量和分娩前HAART的持续时间与传播显着相关，但入组时的CD4细胞计数则不然。母乳喂养的中位时间为 24 周。 Mitra Plus 研究中的传播率约为 Petra 试验组 A 中母乳喂养人群在分娩后 6 个月时传播率的一半（调整后相对风险 = 0.49，P < 0.001）。 18 个月时，Mitra Plus 研究中的 HIV 感染或死亡综合结果显着低于 Petra 试验 A 组的母乳喂养人群（调整后相对风险 = 0.61，P = 0.007）。在 429 名 NVP 暴露女性中，6.5% 出现了 NVP 相关的皮肤粘膜皮疹。 NVP 相关的 3 级或 4 级肝毒性的发生率较低（0.5%）。结论：在妊娠晚期和母乳喂养期间对 HIV 感染母亲进行 HAART 导致产后 HIV 传播率较低，这与之前在达累斯萨拉姆进行的 Mitra 研究中使用 3TC 进行婴儿预防的母乳喂养期间所证明的情况类似。对于自身健康不需要HAART的母乳喂养母亲，应进一步评估使用HAART延长产妇预防性预防HIV-1母婴传播的方法，并与婴儿产后抗逆转录病毒预防的安全性和成本效益进行比较。
Objective: The main aim of this study was to reduce breast-milk transmission of HIV-1 by treating HIV-1-infected women with highly active antiretroviral therapy (HAART) during breastfeeding.Methods: Mina. Plus was an open-label, nonrandomized, prospective cohort study HIV-1-infected pregnant women in Dar es Salaam were treated with zidovudine (ZDV) + lamivudine (3TC) + nevirapine (NVP). NVP was later replaced by nelfinavir for mothers with CD4 cell counts >200 cells per microliter or with adverse reaction to NVP. HAART was initiated at 34 weeks of gestation. For women with symptomatic HIV infection or CD4 cell counts below 200 cells per microliter, HAART was started earlier if possible. Treatment of the mothers was stopped at 6 months except for those mothers who needed HAART for their own health. The infants received ZDV + 3TC for 1 week after birth. Mothers were advised to exclusively breastfeed and to wean abruptly between 5 and 6 months. Transmission of HIV-1 was analyzed using the Kaplan-Meier survival technique. Cox regression was used for comparison with the breastfeeding population of the Petra trial arm A.Results: There were 441 infants included in the analysis of HIV-1 transmission. The cumulative transmission of HIV-1 was 4.1% [95% confidence interval (CI): 2.2 to.6.0] at 6 weeks, 5.0% (95% CI: 2.9 to 7.1) at 6 months, and 6.0% (95% CI: 3.7 to 8.3) at 18 months after delivery. The cumulative risk of HIV transmission between 6 weeks and 6 months was 1.0% and between 6 months and 18 months 1.1%. The cumulative HIV infection or death rate was 8.6% (95% CI: 6.0 to 11.2) at 6 months and 13.6% (95% CI: 10.3 to 16.9) at 18 months after delivery. Viral load at enrollment and duration of HAART before delivery were significantly associated with transmission but CD4 cell count at enrollment was not. The median time of breastfeeding was 24 weeks. The transmission in the Mitra Plus study was about half of the transmission in the breastfeeding population in the Petra trial arm A at 6 months after delivery (adjusted relative hazard = 0.49, P < 0.001). The combined outcome HIV infection or death was significantly lower in the Mitra Plus study than in the breastfeeding population in the Petra trial arm A at 18 months (adjusted relative hazard = 0.61, P = 0.007). NVP-related mucocutaneous rash was demonstrated in 6.5% of 429 NVP-exposed women. The incidence of NVP-related grade 3 or 4 hepatotoxicity was low (0.5%).Conclusions: HAART given to HIV-infected mothers in late pregnancy and during breastfeeding resulted in a low postnatal HIV transmission similar to that previously demonstrated in the Mitra Study in Dar es Salaam using infant prophylaxis with 3TC during breastfeeding. The extended maternal prophylaxis with HAART for prevention of mother-to-child transmission of HIV-1 for breastfeeding mothers who do not need HAART for their own health should be further evaluated and compared with the use of infant postnatal antiretroviral prophylaxis regarding safety and cost-effectiveness.