Detecting primary drug-resistant mutations in Korean HIV patients using ultradeep pyrosequencing

• Published in: Journal of virological methods Vol. 234; pp. 115 - 122
• Main Authors: Cho, Min-Chul, Park, Chang-Wook, Park, Borae G., Oh, Heung-Bum, Choi, Sang-Ho, Choi, Sung-Eun, Cho, Nam-Sun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2016
• Subjects: Adult; Anti-HIV Agents - pharmacology; Blood Donors; Drug resistance; Drug Resistance, Viral - genetics; Genes, pol - genetics; Genotype; High-Throughput Nucleotide Sequencing; HIV; HIV Infections - diagnosis; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus; Humans; Male; Middle Aged; Mutation; Next-generation sequencing; Prevalence; Primary resistance; Republic of Korea; RNA, Viral - blood; RNA, Viral - genetics; Ultradeep pyrosequencing; Korea, Rep; Ultradeep pyrosequencing; Next-generation sequencing; HIV; Drug resistance; Primary resistance
• ISSN: 0166-0934; 1879-0984
• DOI: 10.1016/j.jviromet.2016.04.007

•HIV primary resistance mutation was investigated using UDPS in HIV-positive Korean blood donors and treatment naïve chronic patients.•The entire pol region was successfully sequenced from 19 HIV-positive blood donors, and 18 treatment-naïve chronic HIV patients.•The prevalence of HIV primary resistance in HIV-positive blood donors and chronic HIV patients were 63.2% and 44.4%, respectively.•PI drugs demonstrated different patterns, whereas NNRTI, NRTI, and INI drugs showed similar patterns between the two groups.•The information provided by the present study would help to establish future policies or assess HIV patient care in Korea. HIV primary resistance, drug resistance in treatment-naïve patients, is an emerging public health issue. The prevalence of HIV primary resistance mutations down to the level of 1% minor variants was investigated using ultradeep pyrosequencing (UDPS) in HIV-positive Korean blood donors and in treatment naïve chronic patients for the comparison. The entire pol region was sequenced from 25 HIV-positive blood donors, and 18 treatment-naïve chronic HIV patients. UDPS was successful in 19 blood donors and 18 chronic patients. In total, 1,011,338 sequence reads were aligned, and 28,093 sequence reads were aligned on average per sample. The prevalence of HIV primary resistance mutations in the HIV-positive blood donors and chronic HIV patients were 63.2% and 44.4% according to UDPS, respectively. Protease inhibitor (PI) drugs demonstrated different patterns in HIV-positive blood donors and chronic HIV patients, whereas non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors (NRTI), and integrase inhibitor (INI) drugs showed similar patterns between the two groups. Higher level of primary resistance prevalence was observed mainly because UDPS method could detect mutations in minor variants with 1–10% frequency. The higher resistance prevalence was observed in HIV-positive blood donors than in chronic patients. Considering that treatments for HIV-infected patients were recently amended to start at an earlier stage, information about degree of drug resistance to each drug between the two groups would help to establish future policies, design additional clinical trials, assess HIV patient care in Korea.