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

Author(s): Uluhan Sili*, Burak Aksu, Aysun Tekin, Ufuk Hasdemir, Guner Soyletir, Volkan Korten.

Journal Name: Current HIV Research

Volume 16 , Issue 3 , 2018

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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.

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Article Details

VOLUME: 16
ISSUE: 3
Year: 2018
Page: [216 - 221]
Pages: 6
DOI: 10.2174/1570162X16666180910130112

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