Shaomin Yang

Recombination form and epidemiology of HIV-1 unique recombinant strains identified in Yunnan, China.

Several studies identified HIV-1 recombination in some distinct areas in Yunnan, China. However, no comprehensive studies had been fulfilled in the whole province up to now. To illustrate the epidemiology and recombination form of Unique Recombinant Forms (URFs) circulating in Yunnan, 788 HIV-1 positive individuals residing in 15 prefectures of Yunnan were randomly enrolled into the study. Full-length gag and pol genes were amplified and sequenced. Maximum likelihood tree was constructed for phylogenetic analysis. Recombinant breakpoints and genomic schematics were identified with online software jpHMM. 63 (10.2%) unique recombinant strains were identified from 617 strains with subtypes. The URFs distributed significantly differently among prefectures (Pearson chi-square test, P<0.05). IDUs contained more URFs than sexual transmitted population (Pearson chi-square test, P<0.05). Two main recombinant forms were identified by considering the presence of CRF01_AE segments in full length gag-pol genes, which were B′/C and B′/C/CRF01-AE recombinants. Three clusters were identified in the ML tree which contained more than three sequences and supported by high bootstrap values. One CRF was identified. Many of URFs contained identical breakpoints. The results will contribute to our understanding on HIV recombination and provide clues to the identification of potential CRFs in China.

Different Distribution of HIV-1 Subtype and Drug Resistance Were Found among Treatment Naïve Individuals in Henan, Guangxi, and Yunnan Province of China

Yunnan, Guangxi and Henan are the provinces with the most severe HIV epidemic in China, which were also among the first group of areas providing free ART in 2004. However, little comprehensive data are available on prevalence of HIV subtype and baseline drug resistance in drug-naïve populations. In this study, 1746 treatment-naïve HIV-positive individuals were randomly selected from new-reported cases in Henan, Guangxi and Yunnan. Among of them, subtypes and drug resistance of 1159 strains were determined by amplifying and sequencing full-length pol genes. Significantly different distributions of HIV subtypes prevalent in three provinces were identified (P<0.01). CRF08_BC was found dominant in Yunnan (59.8%), while CRF01_AE was dominant in Guangxi (77.3%) and subtype B was dominant in Henan province (93.9%). The total prevalence of drug resistance was 7.1%. The highest prevalence of HIV drug resistance was found in Henan (12.2%), followed by Yunnan (5.6%) and Guangxi (3.3%). The results of this study suggest that genetic drug-resistance should be tested before initiation of ART in China, especially in Henan province. Furthermore, the prevalence of HIV drug resistant strains should be considered separately in different areas in China before the change of different free ART regimens.

Prevalence and mutation patterns of HIV drug resistance from 2010 to 2011 among ART-failure individuals in the Yunnan Province, China.

Background Assessing the prevalence of HIV-1 drug-resistance and the mutation patterns associated with resistance in the geographical regions implementing free antiretroviral therapy (ART) in China is necessary for preventing the spread of resistant strains and designing the regimens for the subsequent therapies with limited resources. Methods Plasma samples in different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to December 2011. Genotyping of drug-resistant individuals was conducted using an in-house assay on plasma samples. Viral load, CD4 T cell counts and demographic data were obtained from medical records and an administered questionnaire. Results A total of 609 pol sequences (515 ART-failure and 94 therapy-naïve individuals) derived from 664 samples were obtained. The prevalence of drug-resistance was 45.1% in the ART-failure individuals. Of these, 26.8% harbored HIV strains dually resistant to nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors, and 14.8% harbored HIV strains resistant to only one drug category. Mutations such as M184V/I, K103N, V106A, Y181C and G190A were common among the ART-failure individuals, and the frequencies of M184V/I, K103N and V106A were 28.2%, 19.2%, and 22.1%, respectively. The percentages of individuals exhibiting intermediate or high-level resistance to 3TC, FTC, EFV and NVP drugs were 28.4%, 28.2%, 37.3%, and 37.5%, respectively. Factors such as ethnicity, transmission route, CD4 counts, viral load and the duration of ART were significantly correlated with development of drug resistance in the ART-failure individuals. Conclusions The high prevalence of HIV drug-resistance observed among the ART-failure individuals from 2010 to 2011 in Yunnan province should be of increasing concern in regions where the implementation of ART is widespread. Education about the risk factors associated with HIV drug resistance is important for preventing and controlling the spread of HIV drug-resistant strains.

Identification and Characterization of Two New HIV Type 1 Unique (B/C) Recombinant Forms in China

Recombination was most important in the generation of new viral strains and in the increase of HIV diversity. There were more and more new HIV-1 strains. Not only circulating recombinant forms (CRFs) but also unique recombinant forms (URFs) have been reported around the world. CRF07_BC and CRF08_BC were the two predominant CRFs circulated in Yunnan Province, southwest China. In the present study, we identified two new HIV Type 1 unique (B/C) recombinant gorms in Yunnan Province by nucleotide sequencing in two halves of HIV genome. Although the genomic structures of the two B/C recombinants were different from previously identified CRFs (CRF07_BC and CRF08_BC) and URFs in Yunnan Pprovince, they have several common recombination sites with CRF07_BC and CRF08_BC.

Near full-length sequence analysis of a novel HIV-1 C/CRF01_AE recombinant variant from Yunnan, China.

Recombination contributes substantially to the overall genetic complexity of HIV-1, especially in populations in which multiple subtypes circulate. Yunnan is a province in China with most severely HIV epidemic where many subtypes and CRFs of HIV-1 are circulating. In this study, we report a novel HIV-1 recombination involving C and CRF01_AE. The near full-length genome was reverse transcripted and amplified in two halves with the 1 kb overlap regions. The PCR products were sequenced directly after purification. Sequence analysis showed that the majority of the genome was CRF01_AE, three fragments of C subtype were inserted along the genome in gag and pol region. This is the first report of a novel recombination involving subtype C and CRF01_AE in Yunnan, China. More work is needed to check the epidemiologic significance of the new recombination.

Identification and characterization of two human immunodeficiency virus type 1 unique recombinant forms from Yunnan, China

Recombination contributes greatly to the diversity of human immunodeficiency virus type 1 (HIV-1). A large number of recombinant strains have been found in China, particularly in Yunnan, which is considered the HIV-1 epicenter of China. Surveillance of unique recombinant forms is helpful for prediction of new circulating recombinant forms. In this study, we identified two unique recombinant forms of HIV-1 in Yunnan Province. The near full-length genomes of HIV-1 strains were amplified in three parts, and the genomic structures of two strains (12YN10159 and 12YN10192) were analyzed. Strain 12YN10159 was comprised of subtypes C and CRF01_AE, while strain 12YN10192 was comprised of subtypes B and C. Genomic breakpoints were different from all previously reported strains. The data emphasized that more surveillance of unique strains of HIV is needed in Yunnan.

Genetic Diversity and Drug Resistance Among Antiretroviral Treatment-Failed Individuals from 2010 to 2012 in Honghe, China.

The most common antiretroviral treatment (ART) received by individuals infected with HIV-1 in China is the combination therapy, comprised of nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). To assess the prevalence of HIV-1 drug resistance and subtypes in Honghe of Yunnan, China, patient plasmas from ART-failed individuals were collected from January 2010 to December 2012. Genotyping was conducted using an in-house assay on patient plasmas. A total of 254 pol sequences were obtained. The prevalence of drug resistance was 47.2% in ART-failed individuals. Of these drug-resistant individuals, 51.7% harbored HIV strains dually resistant to NRTIs and NNRTIs or protease inhibitors (PIs) (34.2% for NNRTIs and 14.2% for NRTIs). Mutations such as M184V, A62V, T69Ins, K103N, Y181C, and G190A were common among the ART-failed individuals. The frequencies of M184V, A62V, and K103N were 20.5%, 11.0%, and 23.6%, respectively. The most common subtypes in Honghe were CRF08_BC (68.50%) and CRF07_BC (12.20%). The subtypes were almost consistent in different time points for one individual. When receiving ART for 6-12 months, the frequency of HIV-1 drug-resistant variants ranked first. This study shows that the high prevalence of HIV drug resistance observed among the ART-failed individuals should be of increasing concern (monitoring of resistance mutations) in ART regions and facilitate developing novel strategies for prevention and control of HIV infection in China.Abstract The most common antiretroviral treatment (ART) received by individuals infected with HIV-1 in China is the combination therapy, comprised of nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). To assess the prevalence of HIV-1 drug resistance and subtypes in Honghe of Yunnan, China, patient plasmas from ART-failed individuals were collected from January 2010 to December 2012. Genotyping was conducted using an in-house assay on patient plasmas. A total of 254 pol sequences were obtained. The prevalence of drug resistance was 47.2% in ART-failed individuals. Of these drug-resistant individuals, 51.7% harbored HIV strains dually resistant to NRTIs and NNRTIs or protease inhibitors (PIs) (34.2% for NNRTIs and 14.2% for NRTIs). Mutations such as M184V, A62V, T69Ins, K103N, Y181C, and G190A were common among the ART-failed individuals. The frequencies of M184V, A62V, and K103N were 20.5%, 11.0%, and 23.6%, respectively. The most common subtyp...