HAART to Prevent HIV Transmission to Infants In Botswana

描述（由申请人提供）：高效抗逆转录病毒疗法（HAART）正在发展中国家迅速普及，但不同HAART方案在母乳喂养人群中预防母婴艾滋病毒传播（MTCT）的安全性和有效性尚未确定。为了验证我们的假设，即Trizivir（TZV）可能是博茨瓦纳预防MTCT（PMTCT）的简单、安全和有效的策略，560名打算母乳喂养婴儿且CD 4细胞计数> 200个细胞/mm 3的孕妇将随机接受TZV与洛匹那韦/利托那韦（LPV/RTV或Kaletra）/Combivir（CBV），从妊娠20-34周至产后6个月。另外一组约140名基线CD 4计数< 200个细胞/mm 3的妇女将接受奈韦拉平（NVP）/CBV治疗，无限期持续。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个月停止HAART，或在停止母乳喂养时，如果这发生在更早的时候。如果妇女自身的健康需要高效抗逆转录病毒疗法，将通过博茨瓦纳政府的抗逆转录病毒治疗方案无限期地继续使用NVP/CBV。研究中将对女性和婴儿进行随访，直至婴儿达到12个月大。我们认为TZV用于PMTCT时可能表现良好，我们将通过随机分组确定病毒学结局以验证这一假设。我们还认为产前、产时和母乳喂养的母婴传播率将较低，这些将在随机研究的所有婴儿中以及接受NVP/CBV的CD 4计数< 200个细胞/mm 3的妇女所生的婴儿中确定。将在同一诊所进行的一项临床试验中，对接受替代非HAART PMTCT策略的一组婴儿进行MTCT率比较。次要分析将补充这些主要目标，以提供每种HAART方案的风险和益处的完整描述。其他次要分析将探讨妊娠期开始HAART是否会导致婴儿早产和低出生体重;妊娠期LPV/RTV浓度是否较低;血浆和母乳中的低药物浓度是否与这些隔室中的病毒载量和耐药突变以及MTCT相关。博茨瓦纳政府目前向所有CD 4细胞计数< 200个细胞/mm 3的公民提供HAART，并正在考虑向CD 4细胞计数较高的艾滋病毒感染孕妇提供基于TZV的HAART，以防止母婴传播。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）的四个现有地点实施该协议，以帮助指导未来的政策决定。

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.