Arrivé Elise, Newell Marie-Louise, Ekouevi Didier K, Chaix Marie-Laure, Thiebaut Rodolphe, Masquelier Bernard, Leroy Valériane, Perre Philippe Van de, Rouzioux Christine, Dabis François
Unité INSERM 593, Bordeaux, France.
Int J Epidemiol. 2007 Oct;36(5):1009-21. doi: 10.1093/ije/dym104. Epub 2007 May 28.
Single-dose nevirapine (NVP) is the main option for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in countries with limited resources. However, the use of single-dose NVP results in HIV-1 viral resistance which could compromise the success of subsequent treatment of mother and child with antiretroviral combinations that include non-nucleosidic-reverse-transcriptase inhibitors. This systematic review and meta-analysis of summarized data aimed to estimate the proportion of mothers and children with NVP resistance mutations detected in plasma samples 4-8 weeks postpartum after single-dose NVP use for PMTCT.
Systematic search of electronic databases (MEDLINE, PASCAL) and conference proceedings (1997 to February 2006). Inclusion of all studies, without design, place or language restrictions, meeting the following criteria: use of single-dose NVP; viral genotyping performed with standard sequence analyses, between 4 and 8 weeks postpartum, in plasma samples; available public report; report of mothers' median baseline plasma HIV-1 RNA levels. Data extraction by two independent reviewers using a standardized form created for this purpose. Logistic random effect models to obtain pooled estimates. Univariable and multivariable meta-regression to explore sources of heterogeneity.
The pooled estimate of NVP resistance prevalence was 35.7% [95% confidence interval (CI) 23.0-50.6] in women in 10 study arms using single-dose NVP +/- other antepartum antiretrovirals and 4.5% (CI 2.1-9.4) in three study arms providing also postpartum antiretrovirals (adjusted odds ratio 0.08; CI 0.04-0.16). The corresponding estimates in children were 52.6% (CI 37.7-67.0) in seven study arms using single-dose NVP only and 16.5% (CI 8.9-28.3) in eight study arms combining single-dose NVP with other antiretrovirals.
Single-dose NVP is widely used for PMTCT in resource-poor settings, but the burden of viral resistance is high in both women and children. It is substantially lower in studies providing additional postpartum antiretrovirals. The clinical implications of these findings should be further investigated.
在资源有限的国家，单剂量奈韦拉平（NVP）是预防HIV-1母婴传播（PMTCT）的主要选择。然而，使用单剂量NVP会导致HIV-1病毒耐药，这可能会影响随后使用包含非核苷类逆转录酶抑制剂的抗逆转录病毒联合疗法对母婴进行治疗的成功率。本系统评价和汇总数据的荟萃分析旨在估计在单剂量NVP用于PMTCT后产后4至8周血浆样本中检测到NVP耐药突变的母亲和儿童的比例。
系统检索电子数据库（MEDLINE、PASCAL）和会议论文集（1997年至2006年2月）。纳入所有研究，无设计、地点或语言限制，符合以下标准：使用单剂量NVP；产后4至8周在血浆样本中采用标准序列分析进行病毒基因分型；有公开报告；报告母亲基线血浆HIV-1 RNA水平中位数。由两名独立审阅者使用为此目的创建的标准化表格进行数据提取。采用逻辑随机效应模型获得汇总估计值。进行单变量和多变量meta回归以探索异质性来源。
在10个使用单剂量NVP±其他产前抗逆转录病毒药物的研究组中，女性NVP耐药患病率的汇总估计值为35.7%[95%置信区间（CI）23.0 - 50.6]，在3个也提供产后抗逆转录病毒药物的研究组中为4.5%（CI 2.1 - 9.4）（调整比值比0.08；CI 0.04 - 0.16）。在儿童中，仅使用单剂量NVP的7个研究组中的相应估计值为52.6%（CI 37.7 - 67.0），在将单剂量NVP与其他抗逆转录病毒药物联合使用的8个研究组中为16.5%（CI 8.9 - 28.3）。
单剂量NVP在资源匮乏地区广泛用于PMTCT，但女性和儿童的病毒耐药负担都很高。在提供额外产后抗逆转录病毒药物的研究中，该负担明显较低。这些发现的临床意义应进一步研究。
