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Natural polymorphisms associated with integrase inhibitor drug resistance in Estonian HIV-1 CRF06cpx strains

Abstract number: O520

Avi R., Huik K., Sadam M., Karki T., Krispin T., Paap P., Ainsalu K., Schmidt J., Nikitina N., Lutsar I.

Objectives: We aimed to characterise the genetic diversity in integrase (IN) region of HIV-1 circulating in Estonia and to compare their genetic diversity with that of B-subtype viruses in ARV treatment naive (ARV-TN) and experienced (TE) patients.

Methods: A total of 104 ARV-TN (median age 26 y; 57 male; 59 IDU) and 10 TE but none treated with integrase inhibitors (INI) were analysed. All viruses in the latter population had at least one primary RT DRM with the average number of 2.8. The most commonly seen mutations were K103N (n = 9), M184V (n = 7) and V179E (n = 5). A direct sequencing of plasma viral RNA for both populations was performed in IN region (aa 1–289). Subtyping was carried out using phylogenetic analysis (neighbor-joining). The functional positions and the prevalence of reported INI resistance mutations (A38K, H51Y, T66I, V72I, L74IMA, V75I, E92QD, T97A, F121NY, T125KY, A128T, E138K, G140AS, Y143HCR, Q146KR, S147G, Q148H, V151I, S153AY, M154I, N155HS, K156N, E157Q, K160D, G163KR, V165I, V201I, I203M, T206S, S230NR, V249I, R263K and C280Y) were analysed.

Results: The phylogenetic analysis in IN region revealed that a total of 101/114 viruses formed a highly homogenic cluster with CRF06cpx reference sequences, one with CRF02AG, subtype A1 and subtype B each, and 10 remained unclassified.

Mean pair-wise genetic distances in TN and TE populations in IN region of CRF06cpx viruses were similar, 0.014 and 0.016, respectively. In TN population 43 integrase inhibitor DRMs were described, of which the following ones occurred with the highest frequency: V72I in 92%, L74I in 100%, V201I in 97% and T206S in 96% of cases. The amino acid distributions in CRF06cpx viruses at any position of IN region in treated and naive patients were similar. The DDE and HHCC site residues were absolutely conserved in all populations. Compared with the subtype B the presence of IN DRMs V72I, V201I and T206S was more common in CRF06cpx viruses and was seen with the frequency of 17% vs 92%; 11% vs 97% and 9% vs 96%, respectively.

Conclusions: The DRMs in RT region were not associated with the induction of any compensatory mutations in IN region. Compared with subtype B in CRF06cpx viruses the presence of naturally occurring secondary DRMs in IN region was more frequent. The importance of this during the ARV treatment with INI remains to be identified in future clinical trials.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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