[Development of microchips for the detection of mutations of HIV-1 variability to protease inhibitors and the usage results].
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.
Rudinskiĭ
N I
NI
Mikhaĭlovich
V M
VM
Donnikov
M Iu
MIu
Lapa
S A
SA
Sukhanova
A L
AL
Kazennova
E V
EV
Bobkov
A F
AF
Zasedatelev
A S
AS
Pokrovskiĭ
V V
VV
Mirzabekov
A D
AD
D019943:Amino Acid Substitution; D004279:DNA, Viral / Q000235:genetics; D004196:Disease Outbreaks; D024882:Drug Resistance, Viral / Q000235:genetics*; D015751:Genes, pol; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019888:Nelfinavir / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes; D011533:Proviruses / Q000235:genetics; D012426:Russia / Q000453:epidemiology; D012747:Sexual Partners; D015819:Substance Abuse, Intravenous / Q000188:drug therapy / Q000453:epidemiology
D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D015345:Oligonucleotide Probes; D019888:Nelfinavir