Viljoen Johannes, Tuaillon Edouard, Nagot Nicolas, Danaviah Siva, Peries Marianne, Padayachee Prevashinee, Foulongne Vincent, Bland Ruth, Rollins Nigel, Newell Marie-Louise, van de Perre Philippe
aAfrica Centre for Health and Population Studies, University of KwaZulu-Natal, Durban, South Africa bInserm U1058, Université Montpellier 1 cCHRU de Montpellier, Département de Bactériologie-Virologie & Institut de Recherche en Biothérapie and Department of Medical Information, Montpellier, France dRoyal Hospital for Sick Children, Glasgow, UK eDepartment of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa fDepartment of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland gFaculty of Medicine, University of Southampton, Southampton, UK. *Marie-Louise Newell and Philippe van de Perre contributed equally to the writing of this article.
AIDS. 2015 Jan 14;29(2):145-53. doi: 10.1097/QAD.0000000000000527.
Postnatal HIV-1 mother-to-child transmission (MTCT) occurs in spite of antiretroviral therapy. Co-infections in breast milk with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are associated with increased HIV-1 shedding in this compartment. We investigated CMV levels and EBV detection in breast milk as potential risk factors for MTCT of HIV-1 via breastfeeding.
Cell-free HIV-1 RNA, cell-associated HIV-1 DNA, CMV and EBV DNA were quantified in breast milk from 62 HIV-infected mothers and proven postnatal MTCT of HIV-1 via breastfeeding. Controls were 62 HIV-positive mothers with HIV-uninfected infants.
Median (interquartile range) CMV DNA viral load was significantly higher in cases [88,044 (18,586-233,904)] than in controls [11,167 (3221-31,152)] copies/10 breast milk cells (P < 0.001). Breast milk CMV DNA level correlated positively with breast milk HIV-1 RNA level in cases and controls. EBV DNA was detectable in a higher proportion of breast milk samples of cases (37.1%) than controls (16.1%; P = 0.009). HIV-1 MTCT was strongly associated with HIV-1 RNA shedding in breast milk and plasma. In multivariable analysis, every 1 log10 increase in breast milk CMV DNA was associated with a significant 2.5-fold greater odds of MTCT of HIV-1, independent of breast milk and plasma HIV-1 levels; the nearly three-fold increased risk of HIV-1 MTCT with breast milk EBV DNA detection did not reach significance.
We provide the first evidence of an independent association between CMV in breast milk, and postnatal MTCT of HIV-1. This association could fuel persistent shedding of HIV-1 in breast milk in women receiving antiretroviral therapy. EBV DNA detection in breast milk may also be associated with MTCT of HIV-1, but only marginally so.
尽管进行了抗逆转录病毒治疗,但产后仍会发生HIV-1母婴传播(MTCT)。母乳中巨细胞病毒(CMV)和爱泼斯坦-巴尔病毒(EBV)的合并感染与该部位HIV-1脱落增加有关。我们研究了母乳中CMV水平和EBV检测情况,将其作为HIV-1通过母乳喂养发生母婴传播的潜在危险因素。
对62名感染HIV的母亲的母乳进行无细胞HIV-1 RNA、细胞相关HIV-1 DNA、CMV和EBV DNA定量分析,并证实通过母乳喂养发生了产后HIV-1母婴传播。对照组为62名HIV阳性母亲及其未感染HIV的婴儿。
病例组中CMV DNA病毒载量中位数(四分位间距)[88,044(18,586 - 233,904)]显著高于对照组[11,167(3221 - 31,152)]拷贝/10个母乳细胞(P < 0.001)。病例组和对照组中,母乳CMV DNA水平与母乳HIV-1 RNA水平呈正相关。病例组母乳样本中EBV DNA的检出比例(37.1%)高于对照组(16.1%;P = 0.009)。HIV-1母婴传播与母乳和血浆中HIV-1 RNA脱落密切相关。在多变量分析中,母乳CMV DNA每增加1 log10与HIV-1母婴传播几率显著增加2.5倍相关,与母乳和血浆HIV-1水平无关;母乳EBV DNA检测使HIV-1母婴传播风险增加近三倍,但未达到显著水平。
我们首次提供了母乳中CMV与产后HIV-1母婴传播之间存在独立关联的证据。这种关联可能会促使接受抗逆转录病毒治疗的女性母乳中持续存在HIV-1脱落。母乳中EBV DNA检测也可能与HIV-1母婴传播有关,但关联程度较小。