Effects of Daily Cotrimoxazole on Malaria in HIV Exposed, Uninfected Infants

描述(申请人提供)：世界卫生组织建议所有接触艾滋病毒的婴儿在4至6周大时开始联合新诺明预防治疗(CPT)，并继续进行CPT，直到停止母乳喂养并明确排除艾滋病毒感染后至少6周。随着早期婴儿艾滋病毒诊断服务在非洲变得越来越普遍，随着预防母婴艾滋病毒传播(母婴传播)的更有效的药物方案被采用并延长到母乳喂养期，接触艾滋病毒的未感染婴儿的人口正在增加。虽然向感染艾滋病毒的婴儿普遍提供CPT的理由很充分，但人们对普遍提供CPT对感染艾滋病毒的未感染婴儿的影响知之甚少。由于复方新诺明是一种抗疟疾药物，必须了解每日CPT对感染艾滋病毒但未感染的婴儿预防疟疾的影响，以及在疟疾发生时使用它是否会导致寄生虫密度下降。母乳喂养、抗逆转录病毒和营养(BAN)研究(ClinicalTrials.gov编号，NCT00164736)为这项研究提供了最佳研究人群。2004年至2006年期间登记的259名感染艾滋病毒的未感染婴儿符合资格标准，由于遵守马拉维国家指南，没有接受CPT。从2006年开始，马拉维修订了CPT政策，导致626名接触艾滋病毒、未感染的婴儿在4至6周大时开始接受CPT，这些婴儿符合资格标准。该项目的目标是：1)确定CPT对疟疾发病率的影响；2)确定CPT对平均寄生虫血症水平的影响。对于目标1，疟疾将被定义为临床疟疾(临床症状与镜检阳性寄生虫血症)和血点PCR阳性相结合，以确定在12、24和36周龄采集的无症状寄生虫病。对于目标2，我们将结合现有的显微寄生虫血症数据和通过一种新的实时定量聚合酶链式反应从血点中确定的寄生虫病。用广义估计方程建立二项回归和线性回归模型，分别用CPT状态估计疟疾的风险比和CPT状态估计疟疾寄生虫血症的平均差值。这项研究将使我们能够比较从6周大开始每天接受和没有接受复方新诺明治疗的艾滋病毒感染的未感染婴儿在出生后头36周的疟疾发病率(目标1)和疟疾寄生虫血症的平均差异(目标2)。随着预防母婴传播和儿童艾滋病毒情况的持续变化，必须对普遍向感染艾滋病毒的婴儿提供复方新诺明预防疗法的益处进行批判性和科学性的评估。这项研究将增加关于暴露于艾滋病毒的未感染婴儿的CPT的有限证据，并将对马拉维的国家健康儿童、疟疾和艾滋病毒项目产生直接影响。

DESCRIPTION (provided by applicant): The World Health Organization recommends that all HIV-exposed infants begin co-trimoxazole preventive therapy (CPT) between four and six weeks of age, and continue CPT until at least six weeks after cessation of breastfeeding and definitive exclusion of HIV infection. As early infant HIV diagnosis services are becoming more widely available in Africa, and as more efficacious drug regimens for the prevention of mother-to-child HIV transmission (PMTCT) are being adopted and extended through the breastfeeding period, the population of HIV-exposed, uninfected infants is growing. While the case for universal provision of CPT to HIV-infected infants is strong, little is known about the impact of universal provision of CPT to HIV-exposed, uninfected infants. As co-trimoxazole is an antimalarial agent, it will be imperative to know the impact of daily CPT on the prevention of malaria among HIV-exposed but uninfected infants, and whether its use leads to decreased parasite density when malaria episodes do occur. The Breastfeeding, Antiretroviral and Nutrition (BAN) study (ClinicalTrials.gov number, NCT00164736) provides an optimal study population for this research. A total of 259 HIV-exposed, uninfected infants enrolled between 2004 and 2006 met eligibility criteria and did not receive CPT due to compliance with the Malawian national guidelines. Beginning in 2006 Malawi revised their CPT policy resulting in 626 HIV-exposed, uninfected infants enrolled in BAN being initiated on CPT starting at 4 to 6 weeks of age who met eligibility criteria. The goal of this project is to 1) determine the effect of CPT on malaria incidence and 2) determine the effect of CPT on mean parasitemia levels. For Aim 1, malaria will be defined as the combination of clinical malaria (clinical symptoms with documented microscopy positive parasitemia) and PCR positivity on blood spots to determine asymptomatic parasitemias taken at 12, 24, and 36 weeks of age. For Aim 2, we will combine existing microscopic parasitemia data with parasitemias determined by a novel quantitative real time PCR assay from the blood spots. A binomial regression and linear regression model using generalized estimating equations will be used to estimate a risk ratio for malaria by CPT status, and mean difference in malaria parasitemia by CPT status respectively. This research will allow us to compare incidence of malaria (Aim 1) and mean difference in malaria parasitemia (Aim 2) during the first 36 weeks of life among HIV-exposed, uninfected infants that did and did not receive daily co-trimoxazole beginning at 6 weeks of age. As the PMTCT and pediatric HIV landscape continues to change, it is imperative to critically and scientifically assess the benefit of universal provision of co-trimoxazole preventive therapy to HIV-exposed infants. This research will add to the limited body of evidence on CPT in HIV-exposed uninfected infants, and will have direct implications for Malawi's national well-child, malaria, and HIV programs.