Drug resistance mutation profiles of the drug-naïve and first-line regimen-treated HIV-1-infected population of Suzhou, China
- 115 Downloads
Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance (TDR) and acquired drug resistance mutation (ADR) profiles, we collected blood specimens from 127 drug-naïve and 117 first-line drug-treated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified pol fragments from 100 drug-naïve and 20 drug-treated samples. We then determined the drug-resistant mutations to protease (PR) and reverse-transcriptase (RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted (drug-naïve group) and acquired (treated group) resistance mutations, respectively. Six transmitted drug-resistant mutations were found, including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region. Only L76V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.
KeywordsHIV-1 drug resistance mutation first-line regimen China
Unable to display preview. Download preview PDF.
This study was supported by grants from the Natural Science Foundation of Jiangsu Province (BL2013017) and the Suzhou Science and Technology Bureau (SYS201156) to Dr. Feng Qian, the Suzhou Health and Family Planning Commission (LCZX201413) to Ming Li, and the Key National Science and Technology Program in the Thirteen Five-Year Plan Period of China (2017ZX10201102-007-002).
- Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR. 2016. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl J Med, 375: 830–839.CrossRefPubMedPubMedCentralGoogle Scholar
- D’Aquila RT, Johnson VA, Welles SL, Japour AJ, Kuritzkes DR, DeGruttola V, Reichelderfer PS, Coombs RW, Crumpacker CS, Kahn JO, Richman DD. 1995. Zidovudine resistance and HIV-1 disease progression during antiretroviral therapy. AIDS Clinical Trials Group Protocol 116B/117 Team and the Virology Committee Resistance Working Group. Ann Intern Med, 122: 401–408.CrossRefPubMedGoogle Scholar
- Gupta RK, Jordan MR, Sultan BJ, Hill A, Davis DH, Gregson J, Sawyer AW, Hamers RL, Ndembi N, Pillay D, Bertagnolio S. 2012. Global trends in antiretroviral resistance in treatmentnaive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis. Lancet, 380: 1250–1258.CrossRefPubMedPubMedCentralGoogle Scholar
- Hall TA. 1999. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids SympSer 1999, 41: 95–98.Google Scholar
- Han X, Zhang M, Dai D, Wang Y, Zhang Z, Liu J, Geng W, Jiang Y, Takebe Y, Shang H. 2007. Genotypic resistance mutations to antiretroviral drugs in treatment-naive HIV/AIDS patients living in Liaoning Province, China: baseline prevalence and subtype-specific difference. AIDS Res Hum Retroviruses, 23: 357–364.CrossRefPubMedGoogle Scholar
- Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS, Novak NG, Ingersoll R, Sheppard HW, Ray SC. 1999. Fulllength human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol, 73: 152–160.PubMedPubMedCentralGoogle Scholar
- Mackie NE, Dunn DT, Dolling D, Garvey L, Harrison L, Fearnhill E, Tilston P, Sabin C, Geretti AM. 2013. The impact of HIV-1 reverse transcriptase polymorphisms on responses to first-line nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-1-infected adults. Aids, 27: 2245–2253.CrossRefPubMedGoogle Scholar
- Chinese Center for Disease Control and Prevention (China CDC). 2016. Chinese National Free AIDS Antiretroviral Therapy Manual. (In Chinese)Google Scholar
- Qiu T, Ding P, Liu X, Xu J, Guo H, Fu G, Xu X, Huan X. 2014. Epidemiological characteristics of HIV/AIDS patients newly received highly active antiretroviral therapy during 2005–2013 in Jiangsu province. Chin J Epidemiol, 35: 1320–1323. (In Chinese)Google Scholar
- Rhee S-Y, Blanco JL, Jordan MR, Taylor J, Lemey P, Varghese V, Hamers RL, Bertagnolio S, de Wit TFR, Aghokeng AF, et al., 2015. Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis. PLoS Med, 12: e1001810.CrossRefPubMedPubMedCentralGoogle Scholar
- Gandhi RT, Wurcel A, Rosenberg ES, Johnston MN, Hellmann N, Bates M, Hirsch MS, Walker BD. 2003. Progressive reversion of human immunodeficiency virus type 1 resistance mutations in vivo after transmission of a multiply drug-resistant virus. Clin Infect Dis, 37: 1693–1698.CrossRefPubMedGoogle Scholar
- Theys K, Deforche K, Vercauteren J, Libin P, van de Vijver DAMC, Albert J, Åsjö B, Balotta C, Bruckova M, Camacho RJ, et al., 2012. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients. 9.Google Scholar
- UNAIDS. 2015. 2015 China AIDS Response Progress Report. Available: http://www.unaids.org/sites/default/files/country/ documents/CHN_narrative_report_2015.pdfGoogle Scholar
- Wainberg MA, Brenner BG, Turner D. 2005. Changing patterns in the selection of viral mutations among patients receiving nucleoside and nucleotide drug combinations directed against human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother, 49: 1671–1678.CrossRefPubMedPubMedCentralGoogle Scholar
- Wittkop L, Günthard HF, de Wolf F, Dunn D, Cozzi-Lepri A, de Luca A, Kücherer C, Obel N, von Wyl V, Masquelier B, et al., 2011. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study. The Lancet Infectious Diseases, 11: 363–371.CrossRefPubMedGoogle Scholar
- Zhao B, Han X, Xu J, Hu Q, Chu Z, Zhang J, Lu L, Wang Z, Fu J, Chen X, Yan H, Zhuang M, Wang L, Sun A, Zhang CM, Shang H. 2015. Increase of RT-related transmitted drug resistance in non-CRF01_AE among HIV type 1-infected men who have sex with men in the 7 cities of China. J Acquir Immune Defic Syndr, 68: 250–255.CrossRefPubMedGoogle Scholar
- Zhou Y, Lu J, Wang J, Yan H, Li J, Xu X, Zhang Z, Qiu T, Ding P, Fu G, Huan X, Hu H. 2016. Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study. BioMed Research International, 2016: 1752437.PubMedPubMedCentralGoogle Scholar