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Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

ABSTRACT: The rapid spreading of HIV drug resistance is threatening the overall success of free HAART in China. Much work has been done on drug-resistant mutations, however, most of which were based on subtype B. Due to different genetic background, subtypes difference would have an effect on the development of drug-resistant mutations, which has already been proved by more and more studies. In China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE. The depiction of drug resistance mutations in those subtypes will be helpful for the selection of regimens for Chinese. In this study, the distributions difference of amino acids at sites related to HIV drug resistance were compared among subtype B, CRF01_AE, CRF07_BC and CRF08_BC strains prevalent in China. The amino acid composition of sequences belonging to different subtypes, which were obtained from untreated and treated individuals separately, were also compared. The amino acids proportions of 19 sites in RT among subtype B, CRF01_AE and CRF08_BC have significant difference in drug resistance groups (chi-square test, p<0.05). Genetic barriers analysis revealed that sites 69, 138, 181, 215 and 238 were significantly different among subtypes (Kruskal Wallis test, p<0.05). All subtypes shared three highest prevalent drug resistance sites 103, 181 and 184 in common. Many drug resistant sites in protease show surprising high proportions in almost all subtypes in drug-naïve patients. This is the first comprehensive study in China on different development of drug resistance among different subtypes. The detailed data will lay a foundation for HIV treatment regimens design and improve HIV therapy in China.

SUBMITTER: Sui H

PROVIDER: S-EPMC3963863 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

Sui Hongshuai H Gui Tao T Jia Lei L Guo Wei W Han Jingwan J Liu Yongjian Y Bao Zuoyi Z Li Hanping H Li Jingyun J Li Lin L

PloS one 20140324 3

The rapid spreading of HIV drug resistance is threatening the overall success of free HAART in China. Much work has been done on drug-resistant mutations, however, most of which were based on subtype B. Due to different genetic background, subtypes difference would have an effect on the development of drug-resistant mutations, which has already been proved by more and more studies. In China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE. The depiction of drug resistance ...[more]

PMID: 24663120

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Project description:BackgroundComplex mosaic structures of HIV-1 were found in the Democratic Republic of Congo (DRC). Currently, there is limited information on the circulating HIV-1 strains, the distribution of these strains and antiretroviral (ART) resistant viruses in different regions of the country, and the HIV-1 strains harbored by the high-risk groups like female sex workers (FSW) reported to be the source of recombinant and ART resistant viruses.MethodsDried Blood Spots (DBS), collected from 325 infected FSWs in ten cities from 2012 DRC HIV/STI Integrated Biological and Behavioral Surveillance Survey, were tested for HIV-1 genotypes and antiretroviral resistance mutations. Regional segregation of HIV-1 clades was detected using phylogenetics. The significance for differences in HIV-1 subtype and drug resistance mutations were evaluated using Chi-square tests.ResultsThere were 145 (env) and 93 (pol) sequences analyzed. Based on env sequences, the predominant subtype was A1 (44%), and recombinants as defined pol sequences comprised 35% of the total sample. Paired sequences of pol and env from DRC FSW revealed mosaic recombinant in 54% of the sequences. Distinct geographic distributions of different HIV-1 subtypes and recombinants were observed. Subtype A1 was prevalent (40%) in Goma located in the East and significantly higher than in Mbuji-Mayi (p<0.05) in the South-central region, or in Lubumbashi in the South. Antiretroviral resistance was detected in 21.5% of 93 pol sequences analyzed, with the M184I/V and K103N mutations that confer high-level resistance to NRTI and NNRTI, respectively, being the most frequent mutations. However, the K103N mutant viruses were found only in the East.ConclusionHIV-1 variants found in DRC FSW reflect those reported to circulate in the general population from the corresponding geographical locations. HIV-1 mosaic genetics were readily detected in FSW. Importantly, ART resistance mutations to NNRTI and NRTI were common in the DRC sex workers.

Project description:Patients with antiretroviral therapy interruption have a high risk of virological failure when re-initiating antiretroviral therapy (ART), especially those with HIV drug resistance. Next-generation sequencing may provide close scrutiny on their minority drug resistance variant. A cross-sectional study was conducted in patients with ART interruption in five regions in China in 2016. Through Sanger and next-generation sequencing in parallel, HIV drug resistance was genotyped on their plasma samples. Rates of HIV drug resistance were compared by the McNemar tests. In total, 174 patients were included in this study, with a median 12 (interquartile range (IQR), 6-24) months of ART interruption. Most (86.2%) of them had received efavirenz (EFV)/nevirapine (NVP)-based first-line therapy for a median 16 (IQR, 7-26) months before ART interruption. Sixty-one (35.1%) patients had CRF07_BC HIV-1 strains, 58 (33.3%) CRF08_BC and 35 (20.1%) CRF01_AE. Thirty-four (19.5%) of the 174 patients were detected to harbor HIV drug-resistant variants on Sanger sequencing. Thirty-six (20.7%), 37 (21.3%), 42 (24.1%), 79 (45.4%) and 139 (79.9) patients were identified to have HIV drug resistance by next-generation sequencing at 20% (v.s. Sanger, p = 0.317), 10% (v.s. Sanger, p = 0.180), 5% (v.s. Sanger, p = 0.011), 2% (v.s. Sanger, p < 0.001) and 1% (v.s. Sanger, p < 0.001) of detection thresholds, respectively. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. The prevalence of HIV drug resistance in ART interruption was higher than 15% in the survey. Next-generation sequencing was able to detect more minority drug resistance variants than Sanger. There was a sharp increase in minority drug resistance variants when the detection threshold was below 5%.

Dataset Information

Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

Publications

Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

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