The coexistence of secondary PR mutations M36I, K20I and L63H predominates in CRF06-cpx and its next generation recombinant viruses circulating in Estonian treatment-naïve patients
Abstract number: 1733_1410
Avi R., Huik K., Karki T., Sadam M., Paap P., Smidt J., Ainsalu K., Krispin T., Lutsar I.
Objectives: The naturally occurring HIV secondary drug resistance mutations (DRM) in widely spread subtypes (A, B and C) have been adequately described and a high variability between different subtypes has been demonstrated. Such data on circulating recombinant forms (CRF), however, are often missing. We aimed to describe the profile of DRMs in Estonian treatment naive HIV positive subjects carrying predominantly CRF06-cpx viruses or their next generation recombinants.
Methods: A total of 76 treatment-naive subjects (median ages 26 y; 59 male) infected with HIV-1 between 2000 and 2005 were analysed. Of these 62 (82%) were or had been IV drug users and 14 acquired infection via heterosexual route. A direct sequencing of plasma viral RNA was performed in protease (PR), reverse transcriptase (RT), p7 and V3 regions. DRMs were detected by submitting PR and RT sequences to Stanford University HIV Drug Resistance Database; p7 and V3 sequences were subtyped using HIV-Blast application. A footprint analysis of sequenced regions was applied to map recombination patterns between CRF06-cpx and subtype A viruses.
Results: The majority of subjects (96%) carried rare recombinant viruses (CRF06-cpx by 53/76; various recombinant forms of former and A subtype [A06] by 20/76) and only 3/76 had Eastern European subtype A. On footprint analysis of A06 viruses almost all recombination breakpoints were situated in p7 region. A secondary PR resistance mutation M36I was present in all strains. The mutation L63H and K20I were seen in >90% of CRF06-cpx and in approximately 75% of A06 strains. In addition mutations L33V, I93L and L10I were found in 5%, 5%, 7% of CRF06-cpx viruses, respectively. Of all recombinant viruses more than 80% carried 3 or more PR mutations.
Conclusions: The vast majority of CRF06-cpx and its next generation recombinants with Eastern-European subtype A in Estonia carry number of secondary protease mutations of which the combination of M36I, K20I, L63H was most commonly seen.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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