Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique

PLoS One. 2015 Jul 10;10(7):e0131994. doi: 10.1371/journal.pone.0131994. eCollection 2015.

Abstract

Background: Single-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT.

Objectives: To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique.

Methods: One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012) at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/μL (Viroseq). Sequencing was performed with ABI 3100 (Applied Biosystems). Logistic regression modelling was undertaken to identify the factors associated with NVP RAM.

Results: Seventy-nine children had their samples genotyped. Their median age was 7.0 (3-12) months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs) for PMTCT. ARV RAM were detected in 43 (54.4%) of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93-186.34) and with mother's CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02-9.32). In the multivariable analysis the mother's exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33-253.66).

Conclusions: We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers' exposure to PMTCT significantly increased the risk of NVP RAM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Cross-Sectional Studies
  • DNA Mutational Analysis
  • Drug Resistance, Viral / genetics
  • Female
  • Genes, Viral
  • HIV Infections / prevention & control*
  • HIV Infections / transmission
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Infant
  • Infection Control
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Male
  • Mozambique
  • Nevirapine / pharmacology*
  • Nevirapine / therapeutic use

Substances

  • Anti-HIV Agents
  • Nevirapine

Grants and funding

This study was funded by the Associação para a Investigação e Desenvolvimento da Faculdade de Medicina (AIDFM). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.