Medical Microbiology and Immunology

, Volume 208, Issue 2, pp 239–251 | Cite as

High polymorphism rates in well-known T cell epitopes restricted by protective HLA alleles during HIV infection are associated with rapid disease progression in early-infected MSM in China

  • Chuan He
  • Xiaoxu Han
  • Hui Zhang
  • Fanming Jiang
  • Minghui An
  • Bin Zhao
  • Haibo Ding
  • Zining Zhang
  • Tao Dong
  • Hong ShangEmail author
Original Investigation


T cell epitopes restricted by several protective HLA alleles, such as B*57, B*5801, B*27, B*51 and B*13, have been very well defined over the past two decades. We investigated 32 well-known T cell epitopes restricted by protective HLA molecules among 54 Chinese men who have sex with men (MSM) at the early stage of HIV-1 infection. Subjects in our cohort carrying protective HLA types did not exhibit slow CD4 T cell count decline (P = 0.489) or low viral load set points (P = 0.500). Variations occurred in 96.88% (31/32) of the known wild-type epitopes (rate 1.85–100%), and the variation rates of the strains of two CRF01_AE lineages were significantly higher than those of non-CRF01_AE strains (76.82% vs. 48.96%, P = 0.004; 71.27% vs. 8.96%, P = 0.025). Subjects infected with CRF01_AE exhibited relatively rapid disease progression (P = 0.035). Therefore, the lack of wild-type protective T cell epitopes restricted by classic protective HLA alleles in CRF01_AE HIV-1 strains may be one of the reasons why rapid disease progression is observed in Chinese MSM with HIV-1 infection.


Human immunodeficiency virus type 1 Human leukocyte antigen Cytotoxic T lymphocytes Epitope variants Men who have sex with men Disease progression 



Human immunodeficiency virus type 1


Human leukocyte antigen


Men who have sex with men


Enzyme-linked immunosorbent assay


Viral load


Polymerase chain reaction sequence-specific primer



This work was supported by mega projects of national science research for the 13th Five-Year Plan (2017ZX10201101), “Innovation Team Development Program 2016 (IRT_16R70)” of The Ministry of Education, and Natural Science Foundations (81871637,81371787,81701985).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of Medical Research Ethics Committee of the First Affiliated Hospital of China Medical University.

Informed consent

All subjects provided informed consent for this study.


  1. 1.
    McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF (2010) The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol 10:11–23. CrossRefGoogle Scholar
  2. 2.
    Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, Tebit DM, Zhao H, Avila S, Lobritz MA et al (2009) Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog 5:e1000365. CrossRefGoogle Scholar
  3. 3.
    Allen TM, Altfeld M, Geer SC, Kalife ET, Moore C, O’Sullivan KM, DeSouza I, Feeney ME, Eldridge RL, Maier EL et al (2005) Selective escape from CD8 + T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution†. J Virol 79:13239–13249. CrossRefGoogle Scholar
  4. 4.
    McMichael AJ (2006) HIV vaccines. Annu Rev Immunol 24:227–255. CrossRefGoogle Scholar
  5. 5.
    Ranasinghe SR, Kramer HB, Wright C, Kessler BM, di Gleria K, Zhang Y, Gillespie GM, Blais ME, Culshaw A, Pichulik T et al (2011) The antiviral efficacy of HIV-specific CD8(+) T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate. PLoS Pathog 7:e1001341. CrossRefGoogle Scholar
  6. 6.
    Sun J, Zhao Y, Peng Y, Han Z, Liu G, Qin L, Liu S, Sun H, Wu H, Dong T et al (2016) Multiple T-cell responses are associated with better control of acute HIV-1 infection: an observational study. Medicine 95:e4429. CrossRefGoogle Scholar
  7. 7.
    Hanke T (2014) Conserved immunogens in prime-boost strategies for the next-generation HIV-1 vaccines. Expert Opin Biol Ther 14:601–616. CrossRefGoogle Scholar
  8. 8.
    Excler JL, Robb ML, Kim JH (2015) Prospects for a globally effective HIV-1 vaccine. Vaccine 33(Suppl 4):D4–D12. CrossRefGoogle Scholar
  9. 9.
    McMichael A, Mwau M, Hanke T (2002) HIV T cell vaccines, the importance of clades. Vaccine 20:1918–1921. CrossRefGoogle Scholar
  10. 10.
    Santra S, Korber BT, Muldoon M, Barouch DH, Nabel GJ, Gao F, Hahn BH, Haynes BF, Letvin NL (2008) A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys. Proc Natl Acad Sci USA 105:10489–10494. CrossRefGoogle Scholar
  11. 11.
    Gao X, Bashirova A, Iversen AKN, Phair J, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, Altfeld M, O’Brien SJ et al (2005) AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis. Nat Med 11:1290–1292. CrossRefGoogle Scholar
  12. 12.
    Zhang Y, Peng Y, Yan H, Xu K, Saito M, Wu H, Chen X, Ranasinghe S, Kuse N, Powell T et al (2011) Multilayered defense in HLA-B51-associated HIV viral control. J Immunol 187:684–691. CrossRefGoogle Scholar
  13. 13.
    Leslie A, Matthews PC, Listgarten J, Carlson JM, Kadie C, Ndung’u T, Brander C, Coovadia H, Walker BD, Heckerman D et al (2010) Additive contribution of HLA class I alleles in the immune control of HIV-1 infection. J Virol 84:9879–9888. CrossRefGoogle Scholar
  14. 14.
    Martinez-Picado J, Prado JG, Fry EE, Pfafferott K, Leslie A, Chetty S, Thobakgale C, Honeyborne I, Crawford H, Matthews P et al (2006) Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J Virol 80:3617–3623. CrossRefGoogle Scholar
  15. 15.
    Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G, Nowak MA, Giangrande P, Luzzi G, Morgan B, Edwards A et al (1997) Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 3:212–217CrossRefGoogle Scholar
  16. 16.
    Crawford H, Matthews PC, Schaefer M, Carlson JM, Leslie A, Kilembe W, Allen S, Ndung’u T, Heckerman D, Hunter E et al (2010) The hypervariable HIV-1 capsid protein residues comprise HLA-driven CD8 + T-cell escape mutations and covarying HLA-independent polymorphisms. J Virol 85:1384–1390. CrossRefGoogle Scholar
  17. 17.
    Han X, An M, Zhang M, Zhao B, Wu H, Liang S, Chen X, Zhuang M, Yan H, Fu J et al (2013) Identification of 3 distinct HIV-1 founding strains responsible for expanding epidemic among men who have sex with men in 9 Chinese cities. J Acquir Immune Defic Syndr. 64:16–24. CrossRefGoogle Scholar
  18. 18.
    An M, Han X, Xu J, Chu Z, Jia M, Wu H, Lu L, Takebe Y, Shang H (2012) Reconstituting the epidemic history of HIV strain CRF01_AE among men who have sex with men (MSM) in Liaoning, northeastern China: implications for the expanding epidemic among MSM in China. J Virol 86:12402–12406. CrossRefGoogle Scholar
  19. 19.
    Jiang S, He X, Xing H, Ruan Y, Hong K, Cheng C, Hu Y, Xin R, Wei J, Feng Y et al (2012) A comprehensive mapping of HIV-1 genotypes in various risk groups and regions across China based on a nationwide molecular epidemiologic survey. PLoS One 7:e47289. CrossRefGoogle Scholar
  20. 20.
    Pai NP, Ng OT, Lin L, Laeyendecker O, Quinn TC, Sun YJ, Lee CC, Leo YS (2011) Increased rate of CD4 + T-cell decline and faster time to antiretroviral therapy in HIV-1 subtype CRF01_AE infected seroconverters in Singapore. PLoS One 6:e15738. CrossRefGoogle Scholar
  21. 21.
    Time (2000) from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis. Lancet 355:1131–1137. CrossRefGoogle Scholar
  22. 22.
    Li Y, Han Y, Xie J, Gu L, Li W, Wang H, Lv W, Song X, Li Y, Routy JP et al (2014) CRF01_AE subtype is associated with X4 tropism and fast HIV progression in Chinese patients infected through sexual transmission. AIDS 28:521–530. CrossRefGoogle Scholar
  23. 23.
    Chu M, Zhang W, Zhang X, Jiang W, Huan X, Meng X, Zhu B, Yang Y, Tao Y, Tian T et al (2017) HIV-1 CRF01_AE strain is associated with faster HIV/AIDS progression in Jiangsu Province, China. Sci Rep 7:1570. CrossRefGoogle Scholar
  24. 24.
    Brener J, Gall A, Batorsky R, Riddell L, Buus S, Leitman E, Kellam P, Allen T, Goulder P, Matthews PC (2015) Disease progression despite protective HLA expression in an HIV-infected transmission pair. Retrovirology 12:55. CrossRefGoogle Scholar
  25. 25.
    Huang X, Lodi S, Fox Z, Li W, Phillips A, Porter K, Lutsar I, Kelleher A, Li N, Xu X et al (2013) Rate of CD4 decline and HIV-RNA change following HIV seroconversion in men who have sex with men: a comparison between the Beijing PRIMO and CASCADE cohorts. J Acquir Immune Defic Syndr 62:441–446. CrossRefGoogle Scholar
  26. 26.
    Goonetilleke N, Liu MKP, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, Keele BF, Learn GH, Turnbull EL, Salazar MG et al (2009) The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med 206:1253–1272. CrossRefGoogle Scholar
  27. 27.
    Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H et al (2015) Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517:381–385. CrossRefGoogle Scholar
  28. 28.
    McMichael AJ, Rowland-Jones SL (2001) Cellular immune responses to HIV. Nature 410:980–987. CrossRefGoogle Scholar
  29. 29.
    Carlson JM, Du VY, Pfeifer N, Bansal A, Tan VY, Power K, Brumme CJ, Kreimer A, DeZiel CE, Fusi N et al (2016) Impact of pre-adapted HIV transmission. Nat Med 22:606–613. CrossRefGoogle Scholar
  30. 30.
    Pereyra F, Heckerman D, Carlson JM, Kadie C, Soghoian DZ, Karel D, Goldenthal A, Davis OB, DeZiel CE, Lin T et al (2014) HIV control is mediated in part by CD8 + T-cell targeting of specific epitopes. J Virol 88:12937–12948. CrossRefGoogle Scholar
  31. 31.
    Han X, Xu J, Chu Z, Dai D, Lu C, Wang X, Zhao L, Zhang C, Ji Y, Zhang H et al (2011) Screening acute HIV infections among Chinese men who have sex with men from voluntary counseling & testing centers. PLoS ONE 6:e28792. CrossRefGoogle Scholar
  32. 32.
    Huang X, Chen H, Li W, Li H, Jin X, Perelson AS, Fox Z, Zhang T, Xu X, Wu H (2012) Precise determination of time to reach viral load set point after acute HIV-1 infection. J Acquir Immune Defic Syndr 61:448–454. CrossRefGoogle Scholar
  33. 33.
    Jiang F, Han X, Zhang H, Zhao B, An M, Xu J, Chu Z, Dong T, Shang H Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects. BMC Immunol 2016, 17, 28, CrossRefGoogle Scholar
  34. 34.
    Fiebig EW, Wright DJ, Rawal BD, Garrett PE, Schumacher RT, Peddada L, Heldebrant C, Smith R, Conrad A, Kleinman SH et al (2003) Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. Aids 17:1871–1879. CrossRefGoogle Scholar
  35. 35.
    Hu QH, Xu JJ, Zou HC, Liu J, Zhang J, Ding HB, Qian HZ, Li SR, Liu Y, Jiang YJ et al (2014) Risk factors associated with prevalent and incident syphilis among an HIV-infected cohort in Northeast China. BMC Infect Dis 14:658. CrossRefGoogle Scholar
  36. 36.
    Hu QH, Xu JJ, Chu ZX, Zhang J, Yu YQ, Yu H, Ding HB, Jiang YJ, Geng WQ, Wang N et al (2017) Prevalence and determinants of herpes simplex virus type 2 (HSV-2)/syphilis co-infection and HSV-2 mono-infection among human immunodeficiency virus positive men who have sex with men: a cross-sectional study in Northeast China. Jpn J Infect Dis 70:284–289. CrossRefGoogle Scholar
  37. 37.
    Salazar-Gonzalez JF, Bailes E, Pham KT, Salazar MG, Guffey MB, Keele BF, Derdeyn CA, Farmer P, Hunter E, Allen S et al (2008) Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing. J Virol 82:3952–3970. CrossRefGoogle Scholar
  38. 38.
    Zhang H, Zhao B, Han X, Wang Z, Liu B, Lu C, Zhang M, Liu J, Chen O, Hu Q et al (2013) Associations of HLA class I antigen specificities and haplotypes with disease progression in HIV-1-infected Hans in Northern China. Human Immunol 74:1636–1642. CrossRefGoogle Scholar
  39. 39.
    Ngumbela KC, Day CL, Mncube Z, Nair K, Ramduth D, Thobakgale C, Moodley E, Reddy S, de Pierres C, Mkhwanazi N et al (2008) Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure. AIDS Res Hum Retrovir 24:72–82. CrossRefGoogle Scholar
  40. 40.
    Llano A, Williams A, Olvera A, Silva-Arrieta S, Brander C (2013) Best-characterized HIV-1 CTL epitopes: the 2013 update. In: Yusim K et al (eds) HIV Molecular Immunology, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, pp 3–25Google Scholar
  41. 41.
    Honeyborne I, Prendergast A, Pereyra F, Leslie A, Crawford H, Payne R, Reddy S, Bishop K, Moodley E, Nair K et al (2007) Control of human immunodeficiency virus type 1 is associated with HLA-B*13 and targeting of multiple gag-specific CD8 + T-cell epitopes. J Virol 81:3667–3672. CrossRefGoogle Scholar
  42. 42.
    Zhang H, Han X, Zhao B, An M, Wang Z, Jiang F, Xu J, Zhang Z, Dong T, Shang H (2015) Multilayered HIV-1 gag-specific T-cell responses contribute to slow progression in HLA-A*30-B*13-C*06-positive patients. AIDS 29:993–1002. CrossRefGoogle Scholar
  43. 43.
    Goulder PJR, Bunce M, Krausa P, McIntyre K, Crowley S, Morgan B, Edwards A, Giangrande P, Phillips RE, McMichael AJ, Novel (1996) Cross-restricted, conserved, and immunodominant cytotoxic T lymphocyte epitopes in slow progressors in HIV type 1 infection. Aids Res Hum Retrovir 12:1691–1698. CrossRefGoogle Scholar
  44. 44.
    Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, Moore C, Pfafferott KJ, Hilton L et al (2004) Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432:769–775. CrossRefGoogle Scholar
  45. 45.
    Ferre AL, Lemongello D, Hunt PW, Morris MM, Garcia JC, Pollard RB, Yee HF Jr, Martin JN, Deeks SG, Shacklett BL (2010) Immunodominant HIV-specific CD8 + T-cell responses are common to blood and gastrointestinal mucosa, and Gag-specific responses dominate in rectal mucosa of HIV controllers. J Virol 84:10354–10365. CrossRefGoogle Scholar
  46. 46.
    Altfeld M, Kalife ET, Qi Y, Streeck H, Lichterfeld M, Johnston MN, Burgett N, Swartz ME, Yang A, Alter G et al (2006) HLA alleles associated with delayed progression to AIDS contribute strongly to the initial CD8(+) T cell response against HIV-1. PLoS Med 3:e403. CrossRefGoogle Scholar
  47. 47.
    Goulder PJ, Walker BD (2012) HIV and HLA class I: an evolving relationship. Immunity 37:426–440. CrossRefGoogle Scholar
  48. 48.
    Chikata T, Carlson JM, Tamura Y, Borghan MA, Naruto T, Hashimoto M, Murakoshi H, Le AQ, Mallal S, John M et al (2014) Host-specific adaptation of HIV-1 subtype B in the Japanese population. J Virol 88:4764–4775. CrossRefGoogle Scholar
  49. 49.
    Carlson JM, Le AQ, Shahid A, Brumme ZL (2015) HIV-1 adaptation to HLA: a window into virus-host immune interactions. Trends Microbiol 23:212–224. CrossRefGoogle Scholar
  50. 50.
    Kloverpris HN, Leslie A, Goulder P (2015) Role of HLA adaptation in HIV evolution. Front Immunol 6:665. Google Scholar
  51. 51.
    Payne R, Muenchhoff M, Mann J, Roberts HE, Matthews P, Adland E, Hempenstall A, Huang KH, Brockman M, Brumme Z et al (2014) Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence. Proc Natl Acad Sci USA 111:E5393–E5400. CrossRefGoogle Scholar
  52. 52.
    Kawashima Y, Pfafferott K, Frater J, Matthews P, Payne R, Addo M, Gatanaga H, Fujiwara M, Hachiya A, Koizumi H et al (2009) Adaptation of HIV-1 to human leukocyte antigen class I. Nature 458:641–645. CrossRefGoogle Scholar
  53. 53.
    Katoh J, Kawana-Tachikawa A, Shimizu A, Zhu D, Han C, Nakamura H, Koga M, Kikuchi T, Adachi E, Koibuchi T et al (2016) Rapid HIV-1 disease progression in individuals infected with a virus adapted to its host population. PLoS One 11:e0150397. CrossRefGoogle Scholar
  54. 54.
    Kawashima Y, Kuse N, Gatanaga H, Naruto T, Fujiwara M, Dohki S, Akahoshi T, Maenaka K, Goulder P, Oka S et al (2010) Long-term control of HIV-1 in hemophiliacs carrying slow-progressing allele HLA-B*5101. J Virol 84:7151–7160. CrossRefGoogle Scholar
  55. 55.
    Zhang X, Huang X, Xia W, Li W, Zhang T, Wu H, Xu X, Yan H (2013) HLA-B*44 is associated with a lower viral set point and slow CD4 decline in a cohort of Chinese homosexual men acutely infected with HIV-1. Clin Vaccine Immunol 20:1048–1054. CrossRefGoogle Scholar
  56. 56.
    Dong T, Zhang Y, Xu KY, Yan H, James I, Peng Y, Blais ME, Gaudieri S, Chen X, Lun W et al (2011) Extensive HLA-driven viral diversity following a narrow-source HIV-1 outbreak in rural China. Blood 118:98–106. CrossRefGoogle Scholar
  57. 57.
    Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68:4650–4655Google Scholar
  58. 58.
    Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB (1994) Virus-specific CD8 + cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68:6103–6110Google Scholar
  59. 59.
    Christie NM, Willer DO, Lobritz MA, Chan JK, Arts EJ, Ostrowski MA, Cochrane A, Luscher MA, MacDonald KS (2009) Viral fitness implications of variation within an immunodominant CD8 + T-cell epitope of HIV-1. Virology 388:137–146. CrossRefGoogle Scholar
  60. 60.
    Leslie AJ, Pfafferott KJ, Chetty P, Draenert R, Addo MM, Feeney M, Tang Y, Holmes EC, Allen T, Prado JG et al (2004) HIV evolution: CTL escape mutation and reversion after transmission. Nat Med 10:282–289. CrossRefGoogle Scholar
  61. 61.
    Schneidewind A, Brockman MA, Sidney J, Wang YE, Chen H, Suscovich TJ, Li B, Adam RI, Allgaier RL, Mothe BR et al (2008) Structural and functional constraints limit options for cytotoxic T-lymphocyte escape in the immunodominant HLA-B27-restricted epitope in human immunodeficiency virus type 1 capsid. J Virol 82:5594–5605. CrossRefGoogle Scholar
  62. 62.
    Setiawan LC, Gijsbers EF, van Nuenen AC, Kootstra NA (2015) Viral evolution in HLA-B27-restricted CTL epitopes in HIV-1 infected individuals. J Gen Virol. Google Scholar
  63. 63.
    Ammaranond P, van Bockel DJ, Petoumenos K, McMurchie M, Finlayson R, Middleton MG, Davenport MP, Venturi V, Suzuki K, Gelgor L et al (2011) HIV immune escape at an immunodominant epitope in HLA-B*27-positive individuals predicts viral load outcome. J Immunol 186:479–488. CrossRefGoogle Scholar
  64. 64.
    Feeney ME, Tang Y, Roosevelt KA, Leslie AJ, McIntosh K, Karthas N, Walker BD, Goulder PJ (2004) Immune escape precedes breakthrough human immunodeficiency virus type 1 viremia and broadening of the cytotoxic T-lymphocyte response in an HLA-B27-positive long-term-nonprogressing child. J Virol 78:8927–8930. CrossRefGoogle Scholar
  65. 65.
    Miura T, Brockman MA, Schneidewind A, Lobritz M, Pereyra F, Rathod A, Block BL, Brumme ZL, Brumme CJ, Baker B et al (2009) HLA-B57/B*5801 human immunodeficiency virus type 1 elite controllers select for rare gag variants associated with reduced viral replication capacity and strong cytotoxic T-lymphocyte [corrected] recognition. J Virol 83:2743–2755. CrossRefGoogle Scholar
  66. 66.
    Gijsbers EF, Feenstra KA, van Nuenen AC, Navis M, Heringa J, Schuitemaker H, Kootstra NA (2013) HIV-1 replication fitness of HLA-B*57/58:01 CTL escape variants is restored by the accumulation of compensatory mutations in gag. PLoS One 8:e81235. CrossRefGoogle Scholar
  67. 67.
    Pant Pai N, Shivkumar S, Cajas JM (2012) Does genetic diversity of HIV-1 non-B subtypes differentially impact disease progression in treatment-naive HIV-1-infected individuals? A systematic review of evidence: 1996–2010. J Acquir Immune Defic Syndr 59:382–388. CrossRefGoogle Scholar
  68. 68.
    Kiwanuka N, Robb M, Laeyendecker O, Kigozi G, Wabwire-Mangen F, Makumbi FE, Nalugoda F, Kagaayi J, Eller M, Eller LA et al (2009) HIV-1 viral subtype differences in the rate of CD4 + T-cell decline among HIV seroincident antiretroviral naive persons in Rakai District, Uganda. J Acquir Immune Defic Syndrom. Google Scholar
  69. 69.
    Keller M, Lu Y, Lalonde RG, Klein MB (2009) Impact of HIV-1 viral subtype on CD4 + T-cell decline and clinical outcomes in antiretroviral naive patients receiving universal healthcare. Aids. Google Scholar
  70. 70.
    Yuan R, Cheng H, Chen LS, Zhang X, Wang B (2016) Prevalence of different HIV-1 subtypes in sexual transmission in China: a systematic review and meta-analysis. Epidemiol Infect 144:2144–2153. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Chuan He
    • 1
    • 2
    • 3
    • 4
  • Xiaoxu Han
    • 1
    • 2
    • 3
    • 4
  • Hui Zhang
    • 1
    • 2
    • 3
    • 4
  • Fanming Jiang
    • 1
    • 2
    • 3
    • 4
  • Minghui An
    • 1
    • 2
    • 3
    • 4
  • Bin Zhao
    • 1
    • 2
    • 3
    • 4
  • Haibo Ding
    • 1
    • 2
    • 3
    • 4
  • Zining Zhang
    • 1
    • 2
    • 3
    • 4
  • Tao Dong
    • 5
    • 6
  • Hong Shang
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.NHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory MedicineThe First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Key Laboratory of AIDS Immunology of Liaoning ProvinceThe First Affiliated Hospital of China Medical UniversityShenyangChina
  3. 3.Key Laboratory of AIDS ImmunologyChinese Academy of Medical SciencesShenyangChina
  4. 4.Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesHangzhouChina
  5. 5.Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of MedicineOxford UniversityOxfordUK
  6. 6.Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular MedicineOxford UniversityOxfordUK

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