HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission.

HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission.
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DOI:
10.1097/qad.0b013e328302cc11
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发表时间:
2008-07-31
期刊:
AIDS (London, England)
影响因子:
--
通讯作者:
Overbaugh J
Overbaugh J
中科院分区:
其他
文献类型:
--
作者:
Lehman DA;Chung MH;John-Stewart GC;Richardson BA;Kiarie J;Kinuthia J;Overbaugh J

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为减少母婴传播而给予的短程抗逆转录病毒药物对母乳中细胞相关HIV-1 RNA和DNA时间模式的影响尚未明确。肯尼亚妇女接受短程齐多夫定(ZDV)、单剂量奈韦拉平(sdNVP)、ZDV/sdNVP联合治疗或短程高效抗逆转录病毒治疗(HAART)。每周采集母乳样品两至三次,持续4-6周。通过实时PCR定量HIV-1 DNA。通过Gen-Probe HIV-1病毒载量测定定量无细胞和细胞相关RNA水平。在产后第3天至第4周,与ZDV相比,sdNVP、ZDV/sdNVP或HAART治疗显著抑制了母乳中的无细胞HIV-1 RNA水平(P ≤ 0.03)。在4-6周随访期间的任何时间点,治疗组之间的母乳HIV-1 DNA水平(感染细胞水平)均无显著差异。在产后3周,当HAART与ZDV直接比较时,游离RNA水平差异最大(P = 0.0001),ZDV、sdNVP、ZDV/sdNVP和HAART组中每1 × 106个细胞的中位log 10 HIV-1 DNA拷贝数分别为2.78、2.54、2.69和2.31(P = 0.23)。根据线性混合效应模型,HAART与ZDV/sdNVP相比,在第3周期间(3.37 vs 4.02,P = 0.04)以及随着时间的推移,细胞相关HIV-1 RNA水平受到适度抑制。母乳中的无细胞和细胞相关HIV-1 RNA水平在较小程度上受到用于预防母婴传播的抗逆转录病毒疗法的抑制。然而,即使使用HAART,也没有显着减少受感染细胞的储存,这可能有助于母乳HIV-1传播。
The effects of short-course antiretrovirals given to reduce mother-to-child transmission (MTCT) on temporal patterns of cell-associated HIV-1 RNA and DNA in breast milk are not well defined. Women in Kenya received short-course zidovudine (ZDV), single-dose nevirapine (sdNVP), combination ZDV/sdNVP or short-course highly active antiretroviral therapy (HAART). Breast milk samples were collected two to three times weekly for 4–6 weeks. HIV-1 DNA was quantified by real-time PCR. Cell-free and cell-associated RNA levels were quantified by the Gen-Probe HIV-1 viral load assay. Cell-free HIV-1 RNA levels in breast milk were significantly suppressed by sdNVP, ZDV/sdNVP or HAART therapy compared with ZDV between day 3 and week 4 postpartum (P ≤ 0.03). Breast milk HIV-1 DNA levels (infected cell levels) were not significantly different between treatment arms at any timepoint during the 4–6-week follow-up. At 3 weeks postpartum, when the difference in cell-free RNA levels was the greatest comparing HAART directly with ZDV (P = 0.0001), median log10 HIV-1 DNA copies per 1 × 106 cells were 2.78, 2.54, 2.69, and 2.31 in the ZDV, sdNVP, ZDV/sdNVP and HAART arms, respectively (P = 0.23). Cell-associated HIV-1 RNA levels were modestly suppressed in HAART versus ZDV/sdNVP during week 3 (3.37 versus 4.02, P = 0.04), as well as over time according to a linear mixed-effects model. Cell-free and, to a lesser extent, cell-associated HIV-1 RNA levels in breast milk were suppressed by antiretroviral regimens used to prevent MTCT. However, even with HAART, there was no significant reduction in the reservoir of infected cells, which could contribute to breast milk HIV-1 transmission.