Rapid detection of HIV-1 proviral DNA for early infant diagnosis using recombinase polymerase amplification

mBio. 2013 Apr 2;4(2):e00135-13. doi: 10.1128/mBio.00135-13.

Abstract

Early diagnosis and treatment of human immunodeficiency virus type 1 (HIV-1) infection in infants can greatly reduce mortality rates. However, current infant HIV-1 diagnostics cannot reliably be performed at the point of care, often delaying treatment and compromising its efficacy. Recombinase polymerase amplification (RPA) is a novel technology that is ideal for an HIV-1 diagnostic, as it amplifies target DNA in <20 min at a constant temperature, without the need for complex thermocycling equipment. Here we tested 63 HIV-1-specific primer and probe combinations and identified two RPA assays that target distinct regions of the HIV-1 genome (long terminal repeat [LTR] and pol) and can reliably detect 3 copies of proviral DNA by the use of fluorescence detection and lateral-flow strip detection. These pol and LTR primers amplified 98.6% and 93%, respectively, of the diverse HIV-1 variants tested. This is the first example of an isothermal assay that consistently detects all of the major HIV-1 global subtypes.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Primers / genetics
  • DNA, Viral / analysis*
  • DNA, Viral / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Early Diagnosis
  • HIV Infections / diagnosis*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Infant
  • Molecular Diagnostic Techniques / methods*
  • Nucleic Acid Amplification Techniques / methods*
  • Oligonucleotide Probes / genetics
  • Proviruses / genetics
  • Proviruses / isolation & purification*
  • Recombinases / metabolism
  • Sensitivity and Specificity
  • Temperature
  • Virology / methods

Substances

  • DNA Primers
  • DNA, Viral
  • Oligonucleotide Probes
  • Recombinases
  • DNA-Directed DNA Polymerase