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IJE Advance Access originally published online on May 28, 2007
International Journal of Epidemiology 2007 36(5):1009-1021; doi:10.1093/ije/dym104
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Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2007; all rights reserved.
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Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a meta-analysis{dagger}

Elise Arrivé1,2,*, Marie-Louise Newell3, Didier K Ekouevi1,4, Marie-Laure Chaix5, Rodolphe Thiebaut1,6, Bernard Masquelier7,8, Valériane Leroy1,2, Philippe Van de Perre9, Christine Rouzioux5, François Dabis1,2 for the Ghent Group on HIV in Women and Children10

1Unité INSERM 593, Bordeaux, France.
2Institut de Santé Publique, Epidémiologie et Développement (ISPED), Université Victor Segalen, Bordeaux, France.
3Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, UK and Africa Centre for Health and Population Studies, University of KwaZulu Natal, Somkhele, South Africa.
4Programme PACCI and European & Developing Country Clinical Trials Partnership, Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d’Ivoire.
5Laboratoire de Virologie, CHU Necker, Université Paris V, France.
6INSERM U875 Biostatistics, Bordeaux, France.
7Laboratoire de Virologie, CHU Pellegrin, Bordeaux, France.
8EA 2968 Université Victor Segalen, Bordeaux, France.
9Laboratoire de Bactériologie et de Virologie, CHU Arnaud de Villeneuve, Montpellier, France.
10See composition at: www.ghentgroup.org

*Corresponding author. INSERM U593, Institut de Santé Publique, Epidémiologie et Développement (ISPED), Université Victor Segalen Bordeaux 2 33076 Bordeaux Cedex – France. E-mail: Elise.arrive{at}isped.u-bordeaux2.fr


  Abstract

Background 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.

Methods 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.

Results 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.

Conclusions 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.

Keywords PMTCT, HIV-1, nevirapine resistance, meta-analysis, systematic review

{dagger} The study was presented in part at the Third IAS Conference on HIV Pathogenesis and Treatment (Rio De Janeiro) 2005: Abstract TuPe5.2P15.

Accepted 16 April 2007


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