AEGiS-15IAC: Genetic diversity of HIV-1 subtype A and CRF03_AB protease at the territory of the former Soviet Union: emergency and rapid spread of the V77I variant.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Genetic diversity of HIV-1 subtype A and CRF03_AB protease at the territory of the former Soviet Union: emergency and rapid spread of the V77I variant.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrC1011)

Sukhanova AL, Pokrovsky VV, Kazennova EV, Bobkov AF, Weber JN, Roudinskii NI, Mikhailovich VM
Federal AIDS Centre, Moscow, Russian Federation

BACKGROUND: A highly homogeneous subtype A HIV-1 variant (IDU-A) caused the overwhelming majority of HIV-1 infections among IDUs in East Europe. The aim of the study was to characterize polymorphism of the subtype A Protease in the former Soviet Union.

METHODS: During 1996-2003, proviral DNA samples were obtained, with informed consent, from 122 HIV-1+ untreated IDUs from 16 cities of the former Soviet Union. The isolates were defined as IDU-A (n=118) and the CRF03_AB (n=4) using gag/env HMA/sequencing. The region encoding protease (pro) was analyzed using sequencing and an original ProteaseChip hybridization technology.

RESULTS: The mean of pairwise nucleotide distance between 30 pro sequences (26 IDU-A and 4 CRF03_AB) was low (1.24±0.78, range 0.00-3.23). All pro sequences contained no primary resistance mutations. However, 16/26 (61.5%) subtype A isolates bore the V77I substitution known as the secondary mutation determining resistance to Nelfinavir. V77I was also associated with two synonymous substitutions in triplets 31 and 78, suggesting that all V77I-bearing viruses evolved from a single source; their earliest appearance was observed in April 1997, in Tver. Hybridization analysis using ProteaseChip showed that 58/118 (49.2%) HIV-1 isolates studied contained V77I being predominating in Tver, Moscow, Perm, Irkutsk, Yekaterinburg, and Pavlodar. In contrast, the V77I variant was not found in any of 31 DNA samples taken from regions, where the HIV-1 epidemic among IDUs started earlier 1997 (the Ukraine, Moldova, Kazakhstan, and South Russia), as well as in any of 4 CRF03_AB isolates studied.

CONCLUSIONS: The significance of the V77I mutation spreading within the circulating viral pool in Russia and Kazakhstan warrants further analysis. However, the rapid emergence of the V77I HIV-1 strain may influence long-term drug treatment strategies in Russia and Kazakhstan. Monitoring of HIV-1 drug resistance mutations within the former Soviet Union is thus of great importance.

Keywords: AEGIS, HIV-1, USSR, HIV Infections, Variation (Genetics), Genes, env, Genes, gag, Russia, HIV Protease, HIV-1 Reverse Transcriptase, Disease Outbreaks, Endopeptidases, Ukraine, Mutation, Moldova, Kazakhstan, Moscow, Europe, genetics

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