[Development of microchips for the detection of mutations of HIV-1 variability to protease inhibitors and the usage results]. / Razrabotka biologicheskikh mikrochipov dlia vyiavleniia mutatsii ustoichivosti VICH-1 k ingibitoram proteazy i rezul'taty ikh primeneniia.

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.