Citation: Xin-ping LI, Hui XING, Zhe WANG, Xue-feng SI, Lian-en WANG, Hua CHENG, Wei-guo CUI, Shu-lin JIANG, Ling-jie LIAO, Hai-wei ZHOU, Jiang-hong HUANG, Hong PENG, Peng-fei MA, Yi-ming SHAO. Study of HIV-1 Drug Resistance in Patients Receiving Free Antiretroviral Therapy in China .VIROLOGICA SINICA, 2007, 22(3) : 233-240.

Study of HIV-1 Drug Resistance in Patients Receiving Free Antiretroviral Therapy in China

  • Corresponding author: Yi-ming SHAO, yshao@bbn.cn
  • Received Date: 21 December 2006
    Accepted Date: 06 March 2007
    Available online: 01 June 2007

    Fund Project: Molecular epidemiology research and new technologies in HIV surveillance in China sponsored by the 863 program 2006AA02Z418Molecular epidemiology research of HIV-1 Drug resistance in China sponsored by the 973 program 2005CB523103

  • To investigate the prevalence of drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan, China, a total of 431 plasma samples were collected in Queshan county between 2003 and 2004, from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine (Azt+Ddi+Nvp). Personal information was collected by face to face interview. Viral load and genotypic drug resistance were tested. Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program (http://hivdb.stanford.edu). Overall, 38.5% of treatment-naive patients had undetectable plasma viral load (VL), the rate significantly increased to 61.9% in 0 to 6 months treatment patients (mean 3 months) (P<0.005) but again significantly decrease to 38.6% in 6 to 12 months treatment patients (mean 9 months) (P<0.001) and 40.0% in patients receiving more than 12 months treatment (mean 16 months) (P<0.005). The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%, 48.6%, 70.8%, 72.3% in treatment-na?ve, 0 to 6 months treatment, 6 to 12 months treatment, and treatment for greater than 12 months patients, respectively. No mutation associated with resistance to Protease inhibitor (PI) was detected in this study. Nucleoside RT inhibitor (NRTI) mutations always emerged after non-nucleoside RT inhibitor (NNRTI) mutations, and were only found in patients treated for more than 6 months, with a frequency less than 5%, with the exception of mutation T215Y (12.8%, 6/47) which occurred in patients treated for more than 12 months. NNRTI mutations emerged quickly after therapy begun, and increased significantly in patients treated for more than 6 months (P<0.005), and the most frequent mutations were K103N, V106A, Y181C, G190A. There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan,Henan. The drug resistance strains were highly prevalent in antiretroviral-treated patients, and increased with the continuation of therapy, with many patients encountering virological failure after 6 months therapy.

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    2. Conway B, Wainberg M A, Hall D, et al. 2001. Development of drug resistance in patients receiving combinations of zidovudine, didanosine and nevirapine. AIDS, 15 (10): 1269-1274.
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    6. Johnson A, Brun-Vézinet F, Clotet B, et al. 2005. Update of the Drug Resistance Mutations in HIV-1: 2005. Top HIV Med, 13 (1): 51-57.

    7. Kantor R, Katzenstein D. 2004. Drug resistance in nonsubtype B HIV-1.J Clin Virol, 29: 152-159.
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    8. Kantor R, Shafer R W, Follansbee S, et al. 2004. Evolution of resistance to drugs in HIV-1-infected patients failing antiretroviral therapy. AIDS, 18 (11): 1503-1511.
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    9. Li J Y, Li H P, Li L, et al. 2005. Prevalence and evolution of drug resistance HIV-1 variants in Henan, China. Cell Res, 15 (11-12): 843-849.
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    13. Selmi B, Deval J, Alvarez K, et al. 2003. The Y181C substitution in 3'-azido-3'-deoxythymidine-resistant human immunodeficiency virus type 1reverse transcriptase suppresses the ATP-mediated repair of the 3'-azido-3'-deoxy-thymidine 5'-monophosphate-terminated primer. J Biol Chem, 278 (42): 40464-40472.
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    Study of HIV-1 Drug Resistance in Patients Receiving Free Antiretroviral Therapy in China

      Corresponding author: Yi-ming SHAO, yshao@bbn.cn
    • 1. State key laboratory of virology, Wuhan Institute of Virology, Chinese Academy of Science, Wuhan 430071, China
    • 2. State key laboratory for Infectious disease prevention and control, Division of Research on Virology and Immunology, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China
    • 3. Henan Center for Disease Control and Prevention, Zhengzhou 450003, China
    • 4. Queshan Center for Disease Control and Prevention, Henan 463200, China
    • 5. Graduate University of Chinese Academy of Sciences, Beijing 100080, China
    Fund Project:  Molecular epidemiology research and new technologies in HIV surveillance in China sponsored by the 863 program 2006AA02Z418Molecular epidemiology research of HIV-1 Drug resistance in China sponsored by the 973 program 2005CB523103

    Abstract: To investigate the prevalence of drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan, China, a total of 431 plasma samples were collected in Queshan county between 2003 and 2004, from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine (Azt+Ddi+Nvp). Personal information was collected by face to face interview. Viral load and genotypic drug resistance were tested. Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program (http://hivdb.stanford.edu). Overall, 38.5% of treatment-naive patients had undetectable plasma viral load (VL), the rate significantly increased to 61.9% in 0 to 6 months treatment patients (mean 3 months) (P<0.005) but again significantly decrease to 38.6% in 6 to 12 months treatment patients (mean 9 months) (P<0.001) and 40.0% in patients receiving more than 12 months treatment (mean 16 months) (P<0.005). The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%, 48.6%, 70.8%, 72.3% in treatment-na?ve, 0 to 6 months treatment, 6 to 12 months treatment, and treatment for greater than 12 months patients, respectively. No mutation associated with resistance to Protease inhibitor (PI) was detected in this study. Nucleoside RT inhibitor (NRTI) mutations always emerged after non-nucleoside RT inhibitor (NNRTI) mutations, and were only found in patients treated for more than 6 months, with a frequency less than 5%, with the exception of mutation T215Y (12.8%, 6/47) which occurred in patients treated for more than 12 months. NNRTI mutations emerged quickly after therapy begun, and increased significantly in patients treated for more than 6 months (P<0.005), and the most frequent mutations were K103N, V106A, Y181C, G190A. There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan,Henan. The drug resistance strains were highly prevalent in antiretroviral-treated patients, and increased with the continuation of therapy, with many patients encountering virological failure after 6 months therapy.