[Development of microchips for the detection of mutations of HIV-1 variability to protease inhibitors and the usage results]

Vopr Virusol. 2004 Nov-Dec;49(6):10-5.
[Article in Russian]

Abstract

An original biochip was constructed for the detection of 34 mutations of HIV-1 resistance to protease. A technology was worked out, which is based on the hybridization of a fluorescence-labeled amplified fragment of the pol gene of the HIV-1 provirus DNA with a set of specific oligonucleotides immobilized in 3-D hydrogel pads of the biological microchip. The biochip was used to analyze 115 samples of the subtype-1 provirus HIV-1 DNA isolated from untreated IDUs and their sexual partners in 15 regions of former USSR countries. Substitution of Val/IIe in position 77 of protease (V771) is known as secondary mutation of resistance to Nelfinavir detected in 55 (47.8%) of 115 HIV-1 variations. Its first appearance was registered in a patient with HIV in April 1997 in Tver, where its carrying variant caused an HIV outbreak. It is demonstrated that the V771-substitution variant, that dominates in Moscow, caused outbreaks in Irkutsk and Yekaterinburg and spread into separate districts of Perm and Perm Region. At the same time, no V771 HIV-1 was detected in any of the HIV studied cases diagnosed before 1998 in Moldova, Ukraine and Rostov Region.

Publication types

  • English Abstract

MeSH terms

  • Amino Acid Substitution
  • DNA, Viral / genetics
  • Disease Outbreaks
  • Drug Resistance, Viral / genetics*
  • Genes, pol
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • HIV Protease Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Nelfinavir / pharmacology
  • Oligonucleotide Array Sequence Analysis*
  • Oligonucleotide Probes
  • Proviruses / genetics
  • Russia / epidemiology
  • Sexual Partners
  • Substance Abuse, Intravenous / drug therapy
  • Substance Abuse, Intravenous / epidemiology

Substances

  • DNA, Viral
  • HIV Protease Inhibitors
  • Oligonucleotide Probes
  • Nelfinavir