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High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China.

ABSTRACT: BACKGROUND:The overall success of Human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy (ART) was heavily challenged upon the occurrence of drug resistance. Dehong Prefecture witnessed not only the first report of HIV-1 infection but also the experimental adoption of antiviral treatment in China. The transmission and epidemic of HIV-1 in Dehong is impacted by cross-border activities. The characteristics of HIV-1 drug resistance among therapy-naïve Burmese entering travelers in Yunnan and their speculated origin are still not clarified. METHODS:Two hundred ninety-eight HIV-1 infected Burmese entering travelers at Dehong ports were recruited between 2003 and 2012. The partial HIV-1 pol gene fragments were amplified and sequenced for the analysis of drug-resistance mutations (DRMs). Phylogenetic analysis on gag-pol gene was conducted to elucidate phylogenetic and evolutionary characteristics of these drug resistant strains. RESULTS:It was figured out that the occurrence ratio of HIV-1 drug resistance among HIV-1 infected entering travelers from Myanmar was up to 12.8%. The resistant mutations covered several types, including one type of PI mutations (L33F), six types of NRTI mutations and seven types of NNRTI. Close genetic relationship was observed in the phylogenetic analysis on gag-pol gene among the drug resistant strains respectively from Dehong, other Yunnan areas, neighboring provinces (Guangxi) and neighboring countries (Thailand and Myanmar). CONCLUSIONS:The findings in this study revealed that HIV drug resistant locus is spreading from the population who is receiving drug-resistance treatment to the new infectors, which indicates the urgency of surveillance work on drug resistance among the migrant population with high risks of HIV infection.

SUBMITTER: Xuan Q

PROVIDER: S-EPMC5941624 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere are few data on the prevalence of WHO transmitted drug resistance mutations (TDRs) that could affect treatment responses to first line antiretroviral therapy (ART) in Hunan Province, China.ObjectiveDetermine the prevalence of WHO NRTI/NNRTI/PI TDRs in ART-naïve subjects in Hunan Province by deep sequencing.MethodsART-naïve subjects diagnosed in Hunan between 2010-2011 were evaluated by deep sequencing for low-frequency HIV variants possessing WHO TDRs to 1% levels. Mutations were scored using the HIVdb.stanford.edu algorithm to infer drug susceptibility.ResultsDeep sequencing was performed on samples from 90 ART-naïve subjects; 83.3% were AE subtype. All subjects had advanced disease (average CD4 count 134 cells/mm3). Overall 25.6%(23/90) of subjects had HIV with major WHO NRTI/NNRTI TDRs by deep sequencing at a variant frequency level ≥ 1%; 16.7%(15/90) had NRTI TDR and 12.2%(11/90) had a major NNRTI TDR. The majority of NRTI/NNRTI mutations were identified at variant levels <5%. Mutations were analyzed by HIVdb.stanford.edu and 7.8% of subjects had variants with high-level nevirapine resistance; 4.4% had high-level NRTI resistance. Deep sequencing identified 24(27.6%) subjects with variants possessing either a PI TDR or hivdb.stanford.edu PI mutation (algorithm value ≥ 15). 17(19.5%) had PI TDRs at levels >1%.ConclusionsART-naïve subjects from Hunan Province China infected predominantly with subtype AE frequently possessed HIV variants with WHO NRTI/NNRTI TDRs by deep sequencing that would affect the first line ART used in the region. Specific mutations conferring nevirapine high-level resistance were identified in 7.8% of subjects. The majority of TDRs detected were at variant levels <5% likely due to subjects having advanced chronic disease at the time of testing. PI TDRs were identified frequently, but were found in isolation and at low variant frequency. As PI/r use is infrequent in Hunan, the existence of PI mutations likely represent AE subtype natural polymorphism at low variant level frequency.

Project description:Yunnan Province, China is thought to be the original source of biovar Orientalis of Yersinia pestis, the causative agent of the third plague pandemic that has spread globally since the end of the 19th century. Although encompassing a large area of natural plague foci, Y. pestis strains have rarely been found in live rodents during surveillance in Yunnan, and most isolates are from rodent corpses and their fleas. In 2017, 10 Y. pestis strains were isolated from seven live rodents and three fleas in Heqing County (HQ) of Yunnan. These strains were supposed to have low virulence to local rodents Eothenomys miletus and Apodemus chevrieri because the rodents were healthy and no dead animals were found in surrounding areas, as had occurred in previous epizootic disease. We performed microscopic and biochemical examinations of the isolates,and compared their whole-genome sequences and transcriptome with those of 10 high virulence Y. pestis strains that were isolated from the adjacent city (Lijiang). We analyzed the phenotypic, genomic, and transcriptomic characteristics of live rodent isolates. The isolates formed a previously undefined monophyletic branch of Y. pestis that was named 1.IN5. Six SNPs, two indels, and one copy number variation were detected between live rodent isolates and the high virulence neighbors. No obvious functional consequence of these variations was found according to the known annotation information. Among the genes that were differentially expressed between the live rodent isolates and their high virulence neighbors, we detected five iron transfer-related genes that were significantly up-regulated in live rodent isolates compared with high virulence isolates (|log2 (FC) | >1, p.adjust <0.05), indicating these genes may be related to the low-virulence phenotype. The novel genotype of Y. pestis reported here provides further insights into the evolution and spread of plague as well as clues that may help to decipher the virulence mechanism of this notorious pathogen.

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High prevalence of HIV-1 transmitted drug resistance among therapy-naive Burmese entering travelers at Dehong ports in Yunnan, China.

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