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Assessment of Transmitted HIV-1 Drug Resistance Mutations Using Ultra- Deep Pyrosequencing in a Turkish Cohort

[ Vol. 16 , Issue. 3 ]

Author(s):

Uluhan Sili*, Burak Aksu, Aysun Tekin, Ufuk Hasdemir, Guner Soyletir and Volkan Korten   Pages 216 - 221 ( 6 )

Abstract:


Background: Antiretroviral treatment (ART) reduces morbidity and mortality caused by human immunodeficiency virus (HIV) infection; however, the emergence of drug-resistant strains poses an important obstacle to treatment success. Using conventional sequencing methods to determine antiretroviral resistance, mutations present in ≥20% of quasispecies can be identified, but drug-resistant minority variants can lead to virologic failure.

Objective: We aimed to assess transmitted drug resistance mutations (TDRMs) within minority variants using ultra-deep pyrosequencing (UDPS).

Method: Treatment-naive adult patients were included in this observational study. Surveillance TDRMs were classified as ≥20% or at minority variant level (≥2% – <20%). Genotypic sensitivity score calculated by using all pre-treatment drug resistance mutations (PDRMs) was also evaluated.

Results: Thirty-six patients were analyzed. Any TDRM at ≥20% level was detected in 8.3% of the patients (n=3). This prevalence increased to 30.6% (n=11) with the inclusion of minority variants. All non-nucleoside reverse transcriptase inhibitor and protease inhibitor-related TDRMs were within minority variants. The genotypic sensitivity score of rilpivirine-based regimens was considerably diminished when minority variants were included in the PDRM analysis.

Conclusion: UDPS was used for the first time to assess TDRM in a Turkish HIV cohort and uncovered several mutations hidden within minority variants. UDPS may be preferred to detect PDRMs for avoiding virologic failure with rilpivirine-based ART regimens.

Keywords:

Antiretroviral drug resistance, human immunodeficiency virus, minority variants, rilpivirine resistance, transmitted drug resistance, ultra-deep pyrosequencing.

Affiliation:

Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Marmara University, Istanbul, Department of Medical Microbiology, School of Medicine, Marmara University, Istanbul, Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Marmara University, Istanbul, Department of Medical Microbiology, School of Medicine, Marmara University, Istanbul, Department of Medical Microbiology, School of Medicine, Marmara University, Istanbul, Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Marmara University, Istanbul

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