Detecting primary drug-resistant mutations in Korean HIV patients using ultradeep pyrosequencing.
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.
Department of Laboratory Medicine, Gyeongsang National University Hospital and Gyeongsang National University School of Medicine, Jinju, Korea, South Korea.
Min-Chul
MC
Cho
Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
Chang-Wook
CW
Park
Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
Borae G
BG
Park
Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea. Electronic address: hboh@amc.seoul.kr.
Heung-Bum
HB
Oh
Department of Infectious Diseases, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
Sang-Ho
SH
Choi
Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
Sung-Eun
SE
Choi
Korea Red Cross Blood Service, Korean Red Cross, Seoul, South Korea.
Nam-Sun
NS
Cho
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001782:Blood Donors; D024882:Drug Resistance, Viral / Q000235:genetics*; D015751:Genes, pol / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D056910:Republic of Korea
D019380:Anti-HIV Agents; D012367:RNA, Viral
Drug resistance; HIV; Next-generation sequencing; Primary resistance; Ultradeep pyrosequencing