HAART to Prevent HIV Transmission to Infants In Botswana

描述(申请人提供)：高效抗逆转录病毒疗法(HAART)正迅速在发展中国家获得，但不同HAART方案在母乳喂养人群中预防艾滋病毒母婴传播(MTCT)的安全性和有效性尚未确定。为了验证我们的假设，Trizivir(TZV)可能是一种简单、安全和有效的预防博茨瓦纳母婴传播(PMTCT)的策略，560名打算母乳喂养婴儿且CD4细胞计数为200细胞/mm3的孕妇将被随机分为TZV和Lopinavir/RTV(或Kaletra)/Combivir(CBV)，从怀孕20-34周到产后6个月。另外一组-140名基线CD4计数为200个/mm3的妇女将接受奈维拉平(NVP)/CBV治疗，继续无限期。所有婴儿将接受单剂量(SD)NVP和1个月的齐多夫定(ZDV)预防。妇女将在产后6个月或停止母乳喂养时停止HAART，如果这发生得更早的话。如果女性自身的健康需要HAART，它将通过博茨瓦纳政府的抗逆转录病毒(ARV)治疗计划与NVP/CBV无限期继续进行。这项研究将对妇女和婴儿进行跟踪，直到婴儿达到12个月大为止。我们相信TZV在用于PMTCT时可能表现良好，我们将通过随机ARM来确定病毒学结果以检验这一假说。我们还认为，产前、产中和母乳喂养的母婴传播率将很低，这将在随机研究中的所有婴儿中确定，并将在接受NVP/CBV治疗的CD4计数为200个/mm3的母亲所生的婴儿中确定。在同一临床地点的临床试验中，将与一组接受替代非HAART PMTCT策略的婴儿进行MTCT比率的比较。二次分析将补充这些主要目标，以提供每个HAART方案的风险和好处的完整图景。其他二次分析将讨论怀孕期间开始的HAART是否会导致婴儿早产和低出生体重；怀孕期间LPV/RTV浓度是否较低；以及血浆和母乳中的低药物浓度是否与这些间隔中的病毒载量和耐药性突变以及MTCT有关。博茨瓦纳政府目前向所有CD4细胞计数为200个/mm~3的公民提供HAART，并正在考虑向CD4细胞计数较高的HIV感染孕妇提供TZV HAART用于预防母婴传播。博茨瓦纳政府明确支持在博茨瓦纳-哈佛艾滋病研究所伙伴关系(BHP)现有的四个地点实施该议定书，以帮助指导未来的政策决策。

DESCRIPTION (provided by applicant): Highly active antiretroviral therapy (HAART) is rapidly becoming available in the developing world, but the safety and efficacy of different HAART regimens for preventing mother-to-child HIV transmission (MTCT) in a breastfeeding population has not been determined. To test our hypothesis that Trizivir (TZV) may be a simple, safe, and effective strategy to prevent MTCT (PMTCT) in Botswana, 560 pregnant women who intend to breastfeed their infants, and who have CD4 cell counts > 200 cells/mm3, will be randomized to receive TZV vs. Lopinavir/Ritonavir (LPV/RTV, or Kaletra)/Combivir (CBV) from 20-34 weeks of pregnancy through 6 months postpartum. An additional group of -140 women with baseline CD4 counts < 200 cells/mm3 will receive Nevirapine (NVP)/CBV for treatment, continued indefinitely. All infants will receive single dose (SD) NVP and 1 month of zidovudine (ZDV) prophylaxis. Women will discontinue HAART at 6 months postpartum, or at cessation of breastfeeding if this occurs earlier. If HAART is required for a woman's own health, it will be continued indefinitely with NVP/CBV through the Botswana government's Antiretroviral (ARV) Treatment Program. Women and infants will be followed in the study until infants reach 12 months of age. We believe TZV may perform well when used for PMTCT, and we will determine virologic outcomes by randomization arm to test this hypothesis. We also believe rates of antepartum, intrapartum, and breastfeeding MTCT will be low, and these will be determined among all infants in the randomized study, and among those born to women with CD4 counts < 200 cells/mm3 receiving NVP/CBV. Comparison of MTCT rates will be made with a group of infants who received an alternate non-HAART PMTCT strategy in a clinical trial at the same clinic sites. Secondary analyses will complement these primary objectives to provide a complete picture of the risks and benefits of each HAART regimen. Other secondary analysis will address whether HAART started in pregnancy leads to infant prematurity and low birth weight; whether LPV/RTV concentrations are low in pregnancy; and whether low drug concentrations in plasma and breast milk are associated with viral load and resistance mutations in these compartments, and with MTCT. The Botswana government currently offers HAART to all citizens with CD4 cell counts < 200 cells/mm3, and is considering offering TZV-based HAART to HIV-infected pregnant women with higher CD4 cell counts for PMTCT. The Botswana government has given explicit support for this protocol to occur in four existing Botswana-Harvard AIDS Institute Partnership (BHP) locations to help guide future policy decisions.