Drug resistance in antiretroviral-naive children newly diagnosed with HIV-1 in Manaus, Amazonas

J Antimicrob Chemother. 2017 Jun 1;72(6):1774-1783. doi: 10.1093/jac/dkx025.

Abstract

Objectives: To determine the prevalence of drug resistance mutations (DRM), the prevalence of drug susceptibility [transmitted drug resistance (TDR)] and the prevalence of HIV-1 variants among treatment-naive HIV-infected children in Manaus, Amazonas state, Brazil.

Methods: Children born to HIV-infected mothers and diagnosed with HIV in an HIV reference service centre and with available pol sequence between 2010 and 2015 prior to antiretroviral initiation were included. TDR was identified using the Calibrated Population Resistance Tool. HIV-1 subtypes were defined by Rega and phylogenetic analyses.

Results: One hundred and seventeen HIV-infected children with a median age of 3.7 years were included. Among them, 28.2% had been exposed to some form of prevention of mother-to-child transmission (PMTCT). HIV DRM were present in 21.4% of all children. Among PMTCT-exposed children, 3% had NRTI mutations, 15.2% had NNRTI mutations and 3% had PI mutations. Among PMTCT-unexposed children, 1.2% had NRTI mutations, 21.4% had non-NNRTI mutations and 1.2% had PI mutations. The most common DRM was E138A (8.5%). The prevalence of TDR was 16.2%; 21.1% among PMTCT-exposed children and 14.3% among PMTC-unexposed children. The analysis of HIV-1 subtypes revealed that 80.2% were subtype B, 6.0% were subtype C, 3.4% were subtype F1 and 10.3% were possible unique recombinant forms (BF1, 4.3%; DB, 4.3%; BC, 0.9%; KC, 0.9%).

Conclusions: We report a high prevalence of DRM in this population, including in almost a quarter of children with no reported PMTCT. The high prevalence of TDR observed might compromise ART effectiveness. Results show extensive HIV-1 diversity and expansion of subtype C, which highlights the need for surveillance of HIV-1 subtypes in Amazonas state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Brazil
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Resistance, Multiple, Viral / genetics*
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical
  • Male
  • Mothers
  • Mutation
  • Phylogeny
  • RNA, Viral / blood
  • RNA, Viral / genetics
  • Retrospective Studies
  • Sequence Analysis, DNA
  • Viral Load
  • pol Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • pol Gene Products, Human Immunodeficiency Virus