Analysis of the mutations associated to integrase inhibitor resistance in subtypeB and nonB human immunodeficiency virus type1
Abstract number: P1186
Turriziani O., Montagna C., Falasca F., Russo G., Bucci M., Graziano F., Maida P., Monteleone K., Antonelli L., Antonelli G.
Objective: The integrase inhibitors (e.g. Raltegravir) are a new class of antiretroviral drugs that have recently become available for the treatment of HIV patients. The emergence of mutations that confer resistance to the integrase inhibitors has been observed and characterized but viral polymorphisms at the integrase gene caused by immune selection and/or associated with non-subtype B is not completely understood. Here we plan to study the genotypic resistance pattern associated to integrase inhibitor resistance in plasma-HIV RNA derived from B and non B HIV-1 infected individuals.
Methods: Thirty integrase inhibitors naïve HIV-1 infected patients were studied. Twenty non-B HIV-1 samples were collected from patients from Cameroon and 10 subtype-B HIV-1 samples derived from Italian patients. RNA was extracted from 140 mL of plasma using a QIAmp Viral RNA kit (Qiagen, Milan, Italy) following the manufacturer's instructions. Sequencing was undertaken using CLIP, a DNA sequencing technique for direct sequencing of small quantities of amplified template (Open Kit-TruGene HIV-1, Siemens Healthcare Diagnostics).
Results: Among the 20 non B strains the subtype, the distribution was as follows: 10 subtypes CRF02_AG, 3 subtypes CRF02_AE, 3 subtypes D, 1 subtype CRF11_cpx, 1 subtype F2 and 2 subtypes G. No major mutations associated with resistance to integrase inhibitor were detected in HIV-1 subtype B samples. On the contrary major mutations were found in non-B subtype samples. Specifically, 25% of samples showed Y143 H/R/C mutation (4 CRF02_AG and 2 CRF02_AE) and at the same position the Y143S polymorphism was detected in all non-B strain except in subtype F and G. Interestingly in 1 sample belong to subtype G the Q148H pathway (Q148H+E138A+G140S) was found. Other mutations detected at the resistance sites were E92D and E157G/K. E92D was found in 10% of subtype B samples and in 5% of non-B strains (1 CRF11_cpx). E157G/K was detected in 10% of B subtype and in 10% of non-B subtype (1CRF01_AE and 1 CRF02_AG).
Conclusions: These findings indicate that integrase inhibitor resistance mutations can be detected in non-B subtype patients in the absence of drug exposure. This underlies the need for studies to further evaluate the role of integrase inhibitors mutations in the management of HAART in HIV patients.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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