Loss of detectability and indeterminate results: Challenges facing HIV infant diagnosis in South Africa's expanding ART programme

Loss of detectability and indeterminate results: Challenges facing HIV infant diagnosis in South Africa's expanding ART programme
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DOI:
10.7196/samj.8322
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发表时间:
2014-08-01
期刊:
SAMJ: South African Medical Journal
影响因子:
--
通讯作者:
Avenant, T
Avenant, T
中科院分区:
其他
文献类型:
--
作者:
Mazanderani, A F Haeri;du Plessis, N M;Avenant, T

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背景资料。已发现,通过快速获得治疗的早期婴儿诊断可以大大降低与艾滋病毒相关的婴儿死亡率和发病率。根据国际标准,目前的南非指南提倡对所有感染艾滋病毒的婴儿在6周大时进行常规的艾滋病毒-1聚合酶链式反应(PCR)检测,并对检测呈阳性的婴儿“快速”进入艾滋病毒治疗方案。重要的是,检测是在通过母婴抗逆转录病毒疗法(ART)预防母婴传播(PMTCT)方面不断努力的背景下进行的。此外,已经开始接受联合抗逆转录病毒治疗(CART)的婴儿可能会重新进行聚合酶链式反应(PCR)检测,以达到“确认性”目的,包括在收养前进行评估。尽管关于PMTCT方案对HIV-1PCR诊断敏感性的影响的数据有限且相互矛盾,但CART可能会损害HIV-1聚合酶链式反应的敏感性。我们描述了三个不同ART暴露的婴儿的病例系列,在这些病例中,HIV的诊断、确认或收养目的重新测试的结果都是不确定的。这些病例表明,抗逆转录病毒疗法可能与艾滋病毒检测能力的丧失有关,从而导致婴儿服用CART的HIV-1聚合酶链式反应结果为“假阴性”。此外,目前的PMTCT做法可能会导致反复不确定的结果,从而导致cART启动的延迟。HIV-1聚合酶链式反应分析的敏感性需要在不同的抗逆转录病毒药物暴露的背景下重新评估,诊断算法应该相应地进行审查。
Background. Early infant diagnosis with rapid access to treatment has been found to reduce HIV-associated infant mortality and morbidity considerably. In line with international standards, current South African guidelines advocate routine HIV-1 polymerase chain reaction (PCR) testing at 6 weeks of age for all HIV-exposed infants and 'fast-track' entry into the HIV treatment programme for those who test positive. Importantly, testing occurs within the context of increasing efforts at prevention of mother-to-child transmission (PMTCT) by means of maternal and infant antiretroviral therapy (ART). In addition, infants already initiated on combination ART (cART) may be retested with PCR assays for 'confirmatory' purposes, including assessment prior to adoption. The potential for cART to compromise the sensitivity of HIV-1 PCR assays has been described, although there are limited and conflicting data regarding the effect of PMTCT regimens on HIV-1 PCR diagnostic sensitivity.Methods. We describe a case series of three infants with different ART exposures in whom HIV diagnosis, confirmation or the result of retesting for adoption purposes were uncertain.Results. These cases demonstrate that ART can be associated with a loss of detectability of HIV, leading to 'false-negative' HIV-1 PCR results in infants on cART. Furthermore, current PMTCT practices may lead to repeatedly indeterminate results with a subsequent delay in initiation of cART.Conclusion. The sensitivity of HIV-1 PCR assays needs to be re-evaluated within the context of different ART exposures, and diagnostic algorithms should be reviewed accordingly.