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The prevalence and determinants of drug-resistance-associated mutations in the HIV-1-infected MSM population of Henan Province in China

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Abstract

To estimate the prevalence of human immunodeficiency virus (HIV) drug resistance (DR) in a population of men who have sex with men (MSM) from Henan Province of China and to identify the DR-associated HIV-1 mutations in these MSM. The HIV-positive status of the MSM subjects in this study was confirmed using ELISA and Western blotting. The MSM subjects were classified into non-treatment group (n = 106) and treatment group (n = 313). CD4+ T-lymphocyte counts were obtained by flow cytometry, and viral load was measured by branched DNA (bDNA) signal amplification assay. HIV-1 genotypic resistance tests were performed by sequence analysis of the HIV-1 protease and reverse transcriptase genes. In the non-treatment group, 15 patients (14.2 %) displayed DR to non-nucleoside reverse transcriptase inhibitor (NNRTI). In the treatment group, the failure rate of viral suppression was 38.33 % and the DR rate was 33.2 %, which was higher than the rate observed in the non-treatment group (P < 0.05). The incidence of mutations corresponding to NNRTI resistance was significantly higher than the incidence of mutations corresponding to nucleoside reverse transcriptase inhibitor (NRTI) resistance (32.9 % vs. 26.5 %) in the cohort. After antiretroviral therapy (ART), the frequencies of K103N, G190A, Y181C, and V106A mutations were highly elevated. Logistic regression analysis results showed that duration of treatment, poor treatment compliance, drug abuse and homosexual orientation are the major risk factors for DR in this MSM population (all P < 0.05). Our results showed that DR-associated mutations in the HIV-1-infected MSM population increased significantly after ART. Furthermore, duration of treatment, poor treatment compliance, drug abuse and homosexual orientation were identified as the risk factors for DR in the MSM population from Henan Province in China.

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References

  1. Hunt PW, Sinclair E, Rodriguez B, Shive C, Clagett B, Funderburg N, Robinson J, Huang Y, Epling L, Martin JN, Deeks SG, Meinert CL, VanNatta ML, Jabs DA, Lederman MM (2014) Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection. J Infect Dis 210:1228–1238

    Article  CAS  PubMed  Google Scholar 

  2. Gagliardo C, Brozovich A, Birnbaum J, Radix A, Foca M, Nelson J, Saiman L, Yin M, Carras-Terzian E, West E, Neu N (2014) A multicenter study of initiation of antiretroviral therapy and transmitted drug resistance in antiretroviral-naive adolescents and young adults with HIV in New York City. Clin Infect Dis 58:865–872

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Friedman MR, Wei C, Klem ML, Silvestre AJ, Markovic N, Stall R (2014) HIV infection and sexual risk among men who have sex with men and women (MSMW): a systematic review and meta-analysis. PLoS One 9:e87139

    Article  PubMed Central  PubMed  Google Scholar 

  4. Angin M, Sharma S, King M, Murooka TT, Ghebremichael M, Mempel TR, Walker BD, Bhasin MK, Addo MM (2014) HIV-1 infection impairs regulatory T-cell suppressive capacity on a per-cell basis. J Infect Dis 210:899–903

    Article  PubMed  Google Scholar 

  5. Grinsztejn B, Hosseinipour MC, Ribaudo HJ, Swindells S, Eron J, Chen YQ, Wang L, Ou SS, Anderson M, McCauley M, Gamble T, Kumarasamy N, Hakim JG, Kumwenda J, Pilotto JH, Godbole SV, Chariyalertsak S, de Melo MG, Mayer KH, Eshleman SH, Piwowar-Manning E, Makhema J, Mills LA, Panchia R, Sanne I, Gallant J, Hoffman I, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Havlir D, Cohen MS, Team HAS (2014) Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect Dis 14:281–290

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Gunthard HF, Aberg JA, Eron JJ, Hoy JF, Telenti A, Benson CA, Burger DM, Cahn P, Gallant JE, Glesby MJ, Reiss P, Saag, Thomas DL, Jacobsen DM, Volberding PA, International Antiviral Society USAP (2014) Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA 312:410–425

    Article  PubMed  Google Scholar 

  7. Vyas KJ, Limneos J, Qin H, Mathews WC (2014) Assessing baseline religious practices and beliefs to predict adherence to highly active antiretroviral therapy among HIV-infected persons. AIDS Care 26:983–987

    Article  PubMed  Google Scholar 

  8. Ingle SM, May MT, Gill MJ, Mugavero MJ, Lewden C, Abgrall S, Fatkenheuer G, Reiss P, Saag MS, Manzardo C, Grabar S, Bruyand M, Moore D, Mocroft A, Sterling TR, D’Arminio Monforte A, Hernando V, Teira R, Guest J, Cavassini M, Crane HM, Sterne JA, Antiretroviral Therapy Cohort C (2014) Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients. Clin Infect Dis 59:287–297

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Liu H, Ma Y, Su Y, Smith MK, Liu Y, Jin Y, Gu H, Wu J, Zhu L, Wang N (2014) Emerging trends of HIV drug resistance in Chinese HIV-infected patients receiving first-line highly active antiretroviral therapy: a systematic review and meta-analysis. Clin Infect Dis 59:1495–1502

    Article  PubMed  Google Scholar 

  10. Castro H, Pillay D, Cane P, Asboe D, Cambiano V, Phillips A, Dunn DT, Resistance UKCGoHD (2013) Persistence of HIV-1 transmitted drug resistance mutations. J Infect Dis 208:1459–1463

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Gupta R, Hill A, Sawyer AW, Pillay D (2008) Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Clin Infect Dis 47:712–722

    Article  PubMed  Google Scholar 

  12. Taniguchi T, Nurutdinova D, Grubb JR, Onen NF, Shacham E, Donovan M, Overton ET (2012) Transmitted drug-resistant HIV type 1 remains prevalent and impacts virologic outcomes despite genotype-guided antiretroviral therapy. AIDS Res Hum Retroviruses 28:259–264

    Article  CAS  PubMed  Google Scholar 

  13. Sampah ME, Shen L, Jilek BL, Siliciano RF (2011) Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance. Proc Natl Acad Sci USA 108:7613–7618

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Harrigan PR, Hogg RS, Dong WW, Yip B, Wynhoven B, Woodward J, Brumme CJ, Brumme ZL, Mo T, Alexander CS, Montaner JS (2005) Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy. J Infect Dis 191:339–347

    Article  CAS  PubMed  Google Scholar 

  15. Parienti JJ, Massari V, Descamps D, Vabret A, Bouvet E, Larouze B, Verdon R (2004) Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy. Clin Infect Dis 38:1311–1316

    Article  CAS  PubMed  Google Scholar 

  16. Pn M (2014) World Medical Association publishes the Revised Declaration of Helsinki. Natl Med J India 27:56

    Google Scholar 

  17. Gilks CF, Crowley S, Ekpini R, Gove S, Perriens J, Souteyrand Y, Sutherland D, Vitoria M, Guerma T, De Cock K (2006) The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 368:505–510

    Article  PubMed  Google Scholar 

  18. WHO Guidelines Approved by the Guidelines Review Committee (2010) Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a Public Health Approach: 2010 revision. World Health Organization, Geneva

  19. Bennett DE, Bertagnolio S, Sutherland D, Gilks CF (2008) The World Health Organization’s global strategy for prevention and assessment of HIV drug resistance. Antivir Ther 13(Suppl 2):1–13

    PubMed  Google Scholar 

  20. Gatanaga H, Ibe S, Matsuda M, Yoshida S, Asagi T, Kondo M, Sadamasu K, Tsukada H, Masakane A, Mori H, Takata N, Minami R, Tateyama M, Koike T, Itoh T, Imai M, Nagashima M, Gejyo F, Ueda M, Hamaguchi M, Kojima Y, Shirasaka T, Kimura A, Yamamoto M, Fujita J, Oka S, Sugiura W (2007) Drug-resistant HIV-1 prevalence in patients newly diagnosed with HIV/AIDS in Japan. Antiviral Res 75:75–82

    Article  CAS  PubMed  Google Scholar 

  21. Eshleman SH, Husnik M, Hudelson S, Donnell D, Huang Y, Huang W, Hart S, Jackson B, Coates T, Chesney M, Koblin B (2007) Antiretroviral drug resistance, HIV-1 tropism, and HIV-1 subtype among men who have sex with men with recent HIV-1 infection. AIDS 21:1165–1174

    Article  PubMed  Google Scholar 

  22. Johnson JA, Li JF, Wei X, Lipscomb J, Irlbeck D, Craig C, Smith A, Bennett DE, Monsour M, Sandstrom P, Lanier ER, Heneine W (2008) Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. PLoS Med 5:e158

    Article  PubMed Central  PubMed  Google Scholar 

  23. Johnson VA, Calvez V, Gunthard HF, Paredes R, Pillay D, Shafer RW, Wensing AM, Richman DD (2013) Update of the drug resistance mutations in HIV-1: March 2013. Top Antivir Med 21:6–14

    PubMed  Google Scholar 

  24. Richman DD (1996) Antiretroviral drug resistance: mechanisms, pathogenesis, clinical significance. Adv Exp Med Biol 394:383–395

    Article  CAS  PubMed  Google Scholar 

  25. Hamers RL, Wallis CL, Kityo C, Siwale M, Mandaliya K, Conradie F, Botes ME, Wellington M, Osibogun A, Sigaloff KC, Nankya I, Schuurman R, Wit FW, Stevens WS, van Vugt M, de Wit TF, PharmAccess African Studies to Evaluate R (2011) HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study. Lancet Infect Dis 11:750–759

    Article  CAS  PubMed  Google Scholar 

  26. Martinez-Cajas JL, Pant-Pai N, Klein MB, Wainberg MA (2008) Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: a systematic review of virologic and biochemical evidence. AIDS Rev 10:212–223

    PubMed  Google Scholar 

  27. Booth CL, Geretti AM (2007) Prevalence and determinants of transmitted antiretroviral drug resistance in HIV-1 infection. J Antimicrob Chemother 59:1047–1056

    Article  CAS  PubMed  Google Scholar 

  28. Chang SY, Chen MY, Lee CN, Sun HY, Ko W, Chang SF, Chang KL, Hsieh SM, Sheng WH, Liu WC, Wu CH, Kao CL, Hung CC, Chang SC (2008) Trends of antiretroviral drug resistance in treatment-naive patients with human immunodeficiency virus type 1 infection in Taiwan. J Antimicrob Chemother 61:689–693

    Article  CAS  PubMed  Google Scholar 

  29. Barth RE, van der Loeff MF, Schuurman R, Hoepelman AI, Wensing AM (2010) Virological follow-up of adult patients in antiretroviral treatment programmes in sub-Saharan Africa: a systematic review. Lancet Infect Dis 10:155–166

    Article  CAS  PubMed  Google Scholar 

  30. Iyidogan P, Anderson KS (2014) Current perspectives on HIV-1 antiretroviral drug resistance. Viruses 6:4095–4139

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Menendez-Arias L (2002) Targeting HIV: antiretroviral therapy and development of drug resistance. Trends Pharmacol Sci 23:381–388

    Article  CAS  PubMed  Google Scholar 

  32. Hosseinipour MC, van Oosterhout JJ, Weigel R, Phiri S, Kamwendo D, Parkin N, Fiscus SA, Nelson JA, Eron JJ, Kumwenda J (2009) The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy. AIDS 23:1127–1134

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Goldsamt LA, Clatts MC, Parker MM, Colon V, Hallack R, Messina MG (2011) Prevalence of sexually acquired antiretroviral drug resistance in a community sample of HIV-positive men who have sex with men in New York City. AIDS Patient Care STDS 25:287–293

    Article  PubMed Central  PubMed  Google Scholar 

  34. Miller V, Larder BA (2001) Mutational patterns in the HIV genome and cross-resistance following nucleoside and nucleotide analogue drug exposure. Antivir Ther 6(Suppl 3):25–44

    PubMed  Google Scholar 

  35. Naeger LK, Margot NA, Miller MD (2001) Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: analysis of enzyme processivity, chain-terminator removal and viral replication. Antivir Ther 6:115–126

    CAS  PubMed  Google Scholar 

  36. Naeger LK, Miller MD (2001) Mechanisms of HIV-1 nucleoside reverse transcriptase inhibitor resistance: is it all figured out? Curr Opin Investig Drugs 2:335–339

    CAS  PubMed  Google Scholar 

  37. White KL, Margot NA, Wrin T, Petropoulos CJ, Miller MD, Naeger LK (2002) Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Antimicrob Agents Chemother 46:3437–3446

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Hamers RL, Siwale M, Wallis CL, Labib M, van Hasselt R, Stevens WS, Schuurman R, Wensing AM, Van Vugt M, Rinke de Wit TF, PharmAccess African Studies to Evaluate R (2010) HIV-1 drug resistance mutations are present in six percent of persons initiating antiretroviral therapy in Lusaka, Zambia. J Acquir Immune Defic Syndr 55:95–101

    Article  CAS  PubMed  Google Scholar 

  39. Decha P, Intharathep P, Udommaneethanakit T, Sompornpisut P, Hannongbua S, Wolschann P, Parasuk V (2011) Theoretical studies on the molecular basis of HIV-1RT/NNRTIs interactions. J Enzyme Inhib Med Chem 26:29–36

    Article  CAS  PubMed  Google Scholar 

  40. Barth RE, Wensing AM, Tempelman HA, Moraba R, Schuurman R, Hoepelman AI (2008) Rapid accumulation of nonnucleoside reverse transcriptase inhibitor-associated resistance: evidence of transmitted resistance in rural South Africa. AIDS 22:2210–2212

    Article  CAS  PubMed  Google Scholar 

  41. Nijhuis M, Deeks S, Boucher C (2001) Implications of antiretroviral resistance on viral fitness. Curr Opin Infect Dis 14:23–28

    Article  CAS  PubMed  Google Scholar 

  42. Martinez-Picado J, Martinez MA (2008) HIV-1 reverse transcriptase inhibitor resistance mutations and fitness: a view from the clinic and ex vivo. Virus Res 134:104–123

    Article  CAS  PubMed  Google Scholar 

  43. Zhang X, Li S, Li X, Li X, Xu J, Li D, Ruan Y, Xing H, Zhang X, Shao Y (2007) Characterization of HIV-1 subtypes and viral antiretroviral drug resistance in men who have sex with men in Beijing. China. AIDS 21(Suppl 8):S59–65

    Article  PubMed  Google Scholar 

  44. Gong J, Wang XQ, Tong X, Shen XH, Yang RG (2011) Emerging trends of drug-resistant HIV-1 among drug-treated patients in former blood donors in Hubei, China: a three-year surveillance from 2004 to 2006. Virol Sin 26:386–392

    Article  PubMed  Google Scholar 

  45. Shen C-H (2014) Crystallographic analysis and molecular modeling studies of HIV-1 protease and drug resistant mutants, Dissertation, Georgia State University. http://scholarworks.gsu.edu/biology_diss/151/

  46. Bangsberg DR (2008) Preventing HIV antiretroviral resistance through better monitoring of treatment adherence. J Infect Dis 197(Suppl 3):S272–278

    Article  PubMed  Google Scholar 

  47. Paredes R, Lalama CM, Ribaudo HJ, Schackman BR, Shikuma C, Giguel F, Meyer WA 3rd, Johnson VA, Fiscus SA, D’Aquila RT, Gulick RM, Kuritzkes DR, Team ACTGAS (2010) Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis 201:662–671

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Altice FL, Kamarulzaman A, Soriano VV, Schechter M, Friedland GH (2010) Treatment of medical, psychiatric, and substance-use comorbidities in people infected with HIV who use drugs. Lancet 376:367–387

    Article  PubMed  Google Scholar 

  49. Werb D, Mills EJ, Montaner JS, Wood E (2010) Risk of resistance to highly active antiretroviral therapy among HIV-positive injecting drug users: a meta-analysis. Lancet Infect Dis 10:464–469

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to acknowledge the reviewers for their helpful comments on this paper.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. The First Department of Infectious Disease, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Jiankang Road, Weihui, 453100, People’s Republic of China

    Li-Juan Hou, Hong-Wei Wang, Shu-Peng Duan & Bao-Sheng Shen

  2. The Second Department of Infectious Disease, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, People’s Republic of China

    Ya Zhuo, Yan-Cai Zhou & Hong-Jie Wu

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  1. Li-Juan Hou
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  2. Hong-Wei Wang
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Correspondence to Bao-Sheng Shen.

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Hou, LJ., Wang, HW., Duan, SP. et al. The prevalence and determinants of drug-resistance-associated mutations in the HIV-1-infected MSM population of Henan Province in China. Arch Virol 160, 2051–2061 (2015). https://doi.org/10.1007/s00705-015-2481-4

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