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

• Published in: Current HIV research Vol. 16; no. 3; p. 216
• Main Authors: Sili, Uluhan, Aksu, Burak, Tekin, Aysun, Hasdemir, Ufuk, Soyletir, Guner, Korten, Volkan
• Format: Journal Article
• Language: English
• Published: Netherlands 01-01-2018
• Subjects: Adult; Aged; Aged, 80 and over; Drug Resistance, Viral; Female; Genotype; High-Throughput Nucleotide Sequencing; HIV Infections - epidemiology; HIV Infections - transmission; HIV Infections - virology; HIV-1 - classification; HIV-1 - genetics; HIV-1 - isolation & purification; Humans; Male; Middle Aged; Mutation; Prevalence; Sequence Analysis, DNA; Turkey - epidemiology; Young Adult; Turkey; Antiretroviral drug resistance; human immunodeficiency virus; ultra-deep pyrosequencing; rilpivirine resistance; minority variants; transmitted drug resistance
• ISSN: 1873-4251
• DOI: 10.2174/1570162X16666180910130112

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