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

描述（由申请人提供）：世界卫生组织建议所有艾滋病毒暴露的婴儿在4至6周龄之间开始复方新诺明预防治疗（CPT），并在停止母乳喂养和明确排除艾滋病毒感染后至少6周继续CPT。随着非洲越来越广泛地提供婴儿艾滋病毒早期诊断服务，以及在母乳喂养期间采用和延长预防母婴艾滋病毒传播的更有效药物方案，暴露于艾滋病毒的未感染婴儿人数正在增加。虽然向感染艾滋病毒的婴儿普遍提供CPT的理由很充分，但对向暴露于艾滋病毒的未感染婴儿普遍提供CPT的影响知之甚少。由于复方新诺明是一种抗疟药，因此必须了解每天使用复方新诺明对艾滋病毒暴露但未感染的婴儿预防疟疾的影响，以及在疟疾发作时使用复方新诺明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）为这项研究提供了一个最佳的研究人群。2004年至2006年期间登记的共有259名暴露于艾滋病毒的未感染婴儿符合资格标准，但由于遵守马拉维国家准则而未接受CPT。从2006年开始，马拉维修订了其CPT政策，使626名接触艾滋病毒的未感染婴儿在符合资格标准的4至6周龄开始接受CPT。该项目的目标是：1)确定CPT对疟疾发病率的影响；2)确定CPT对平均寄生虫病水平的影响。在目标1中，疟疾将被定义为临床疟疾（临床症状伴有显微镜记录的寄生虫血症阳性）和血点PCR阳性的结合，以确定在12、24和36周龄时采集的无症状寄生虫。在Aim 2中，我们将把现有的显微寄生虫病数据与一种新的实时定量PCR法从血斑中测定的寄生虫相结合。基于广义估计方程的二项回归模型和线性回归模型将分别估算CPT状态下疟疾的风险比和CPT状态下疟疾寄生虫病的平均差异。这项研究将使我们能够比较暴露于艾滋病毒的未感染婴儿，从6周龄开始每天服用复方新诺明和不服用复方新诺明的婴儿，在生命的前36周内疟疾发病率（目标1）和疟疾寄生虫病的平均差异（目标2）。随着预防母婴传播和儿童艾滋病毒形势的不断变化，有必要对普遍向艾滋病毒暴露婴儿提供复方新诺明预防治疗的益处进行批判性和科学的评估。这项研究将为有限的证据补充CPT在艾滋病毒暴露的未感染婴儿中的应用，并将对马拉维的国家儿童健康、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.