An early-infant HIV-risk score for targeted HIV testing at birth - South Africa

Abstract
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Background
Early HIV testing is needed to guarantee early HIV treatment success for very young infants, but universal testing is expensive. In this study, we examined the feasibility of using an early-infant HIV-risk score for targeted PCR testing and early diagnosis of HIV.
Methods and findings
We reviewed the maternal and infant characteristics of a cross-sectional sample of HIV exposed newborns at Kalafong Provincial Tertiary Hospital, Gauteng, South Africa. Infants were clinically evaluated and tested for HIV infection by PCR within 72 hours of birth. We quantified associations between HIV infection and individual parameters by fitting univariate and multivariate logistic regression models. We determined sensitivity and specificity for various cut-points of the derived risk scores.
From August 2014 to December 2016, of 15 175 live births, 3356 (22.12%) were born to HIV-infected mothers. We screened 1911 infants, and enrolled 1759 (92%) of these. Mothers who had no antenatal care visits (5.7% (97/1688)) were more likely to give birth to babies who tested PCR positive (p=0.0005). Most mothers (98.8%) knew their HIV status before delivery and were on cART (1626/1704, 95.4%). Virological control varied with HIV viral loads not detectable in 595 (60.15%) of mothers. One in five mothers (217/990, 21.9%) had viral loads greater than 1000 copies/µL. More than a quarter of babies (432/1655, 26.1%) were born at a gestational age <38weeks. Low birth weight (<2.5kg) was documented in 398/1598 (24.55%) and 13/31(40.63%) of the PCR negative and positive infants, respectively (p=0.0329). Fewer than 15% of babies were clinically symptomatic at birth. Growth restriction or small for gestational age were documented in 204/1689 (12.08%) babies, of whom six (6/37, 16.22%) were PCR positive. Symptomatic newborns more frequently tested HIV positive (p=0.0042). The newborn HIV PCR positivity rate was 1.8% (31/1759).
The most significant risk factors for HIV infection in very young infants were detectable maternal HIV viral load, maternal cART duration of <1 month, and an infant that was symptomatic at birth. We included small-for-gestational-age with the above three characteristics in multivariate analyses and developed a two-, three-, and four-risk model, with a predictive probability score of a newborn PCR positive test at 0.28, 0.498, and 0.57 respectively. Sensitivities of the three- and four-risk scores as a probability of 0.02 and 0.04 are 80% and 76%, respectively.
Conclusion
Targeted PCR testing to diagnose HIV infection in very young infants requires access to maternal viral load testing. Even if risk models include other parameters such as maternal cART history, infant birthweight, gestation estimates and symptoms, one-in-five infected infants will not be targeted for testing. At present; we support universal PCR testing at birth within the South African PMTCT context.

摘要
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背景
早期对艾滋病病毒（HIV）的检测对于确保极年轻婴儿的早期HIV治疗成功至关重要，但普遍检测的成本高昂。在本研究中，我们探讨了使用早期婴儿HIV风险评分进行针对性的聚合酶链反应（PCR）检测和早期HIV诊断的可行性。
方法与发现
我们回顾了南非豪登省卡拉丰省立三级医院HIV暴露新生儿的母亲和婴儿特征。婴儿在出生后72小时内进行临床评估和HIV感染PCR检测。我们通过拟合单变量和多变量逻辑回归模型来量化HIV感染与个体参数之间的关联。我们确定了所得风险评分各种截断点的灵敏度和特异性。
从2014年8月到2016年12月，在15,175例活产中，有3,356例（22.12%）的母亲感染了HIV。我们筛查了1,911名婴儿，并从中招募了1,759名（92%）。未进行产前检查的母亲（5.7%（97/1688））更有可能生下PCR检测呈阳性的婴儿（p=0.0005）。大多数母亲（98.8%）在分娩前已知自己的HIV状态，并正在接受持续抗逆转录病毒治疗（cART）（1,626/1,704，95.4%）。病毒学控制因HIV病毒载量不可检测而有所差异，在595名（60.15%）的母亲中。五分之一的母亲（217/990，21.9%）的病毒载量超过1000拷贝/µL。超过四分之一的婴儿（432/1,655，26.1%）在孕周小于38周时出生。低出生体重（<2.5kg）在PCR阴性婴儿中的记录率为398/1,598（24.55%），在PCR阳性婴儿中的记录率为13/31（40.63%）（p=0.0329）。不到15%的婴儿在出生时出现临床症状。生长受限或小于孕周出生的记录在204/1,689名婴儿中（12.08%），其中6名（6/37，16.22%）为PCR阳性。有症状的新生儿更频繁地检测出HIV阳性（p=0.0042）。新生儿HIV PCR阳性率为1.8%（31/1,759）。
极年轻婴儿HIV感染的最显著风险因素为可检测的母体HIV病毒载量、母体cART持续时间小于1个月，以及出生时出现症状的婴儿。我们将具有上述三个特征的早产儿纳入多变量分析，并开发了包含两个、三个和四个风险因素的风险模型，新生儿的PCR阳性测试预测概率评分分别为0.28、0.498和0.57。三个和四个风险评分的灵敏度为0.02和0.04的概率分别为80%和76%。
结论
针对极年轻婴儿进行HIV感染的针对性PCR检测需要获取母体病毒载量检测。即使风险模型包括其他参数，如母体cART病史、婴儿出生体重、孕周估计和症状，仍有五分之一的感染婴儿不会被纳入检测范围。在目前的南非预防母婴传播（PMTCT）背景下，我们支持在出生时进行普遍的PCR检测。