Virologica Sinica

, Volume 33, Issue 3, pp 227–233 | Cite as

Evaluation of Epstein-Barr Virus Salivary Shedding in HIV/AIDS Patients and HAART Use: A Retrospective Cohort Study

  • Yan Yan
  • Yong Ren
  • Renfang Chen
  • Jing Hu
  • Yongjia Ji
  • Junyang Yang
  • Jiayin Shen
  • Lvyin Hu
  • Hao Pei
  • Jun Wang
  • Yuanwang Qiu
  • Hongzhou Lu
  • Lihua Huang
Research Article


Little data is available on the evaluation of the occurrence rates of Epstein-Barr virus (EBV) in saliva and relationship with highly active antiretroviral therapy (HAART) use in HIV/AIDS patients in China. We conducted a retrospective cohort study of EBV serological tests for HIV/AIDS patients who were treated in the hospitals for infectious diseases in Wuxi and Shanghai, China from May 2016 to April 2017. The EBV-seropositive samples were identified by ELISA. EBV-specific primers and probes were used for the quantitative detection of viral DNA from saliva via quantitative real-time polymerase chain reaction. CD4 cell counts of the HIV/AIDS patients were detected by a flow cytometry. A total of 372 HIV/AIDS patients were ultimately selected and categorized for this retrospective cohort study. For EBV IgG and IgM, the HIV/AIDS HAART use (H) and non-HAART use (NH) groups had significantly higher seropositive rates than the HIV-negative control group. The HIV/AIDS (NH) group had the highest seropositive rate (IgG, 94.27%; IgM, 68.98%) and the highest incidence of EBV reactivation or infection. For salivary EBV DNA-positive rates and quantities, the HIV/AIDS (H) (73.69%) and the HIV/AIDS (NH) (100%) groups showed significantly higher values than the HIV-negative control group (35.79%, > twofold). Further, the salivary EBV DNA-negative population had significantly higher CD4 cell counts than the EBV DNA-positive population in the HIV/AIDS (H) group and the HIV/AIDS (NH) groups. Thus, HAART use is beneficial in decreasing the EBV salivary shedding in HIV/AIDS patients and indirectly decreases EBV transmission risk.


Epstein-Barr virus (EBV) Human immunodeficiency virus (HIV) Saliva HIV/AIDS Highly active antiretroviral therapy (HAART) 



We thank Yanping Guo and Xiaojuan Yang from the Department of Medical Instruments of Wuxi Fifth People’s Hospital Affiliated to Jiangnan University for the purchase of reagents. This work was supported by the Grant of Wuxi Technology Bureau Scientific and Technology Project (CSE31N1607), the Wuxi Key Medical Talents Program (ZDRC024), Shanghai Pujiang Program (15PJ1407300), the Wuxi Medical Development Discipline Program (FZXK006, MS201702), the Significant Program from Wuxi Health and Family Planning Commission (z201603), the National High Technology Research and Development Program of China (2014AA021403), the National Natural Science Foundation of China (81571977, 81701550) and the Project from Shanghai Municipal Commission of Health and Family Planning (15GWZK0103).

Author Contributions

HZL, LHH and YY conceived the study. YY, YR, RFC, YJJ, JYY, JW and JH carried out the experiments and formal analysis. YR, RFC, JYS, JYY, YWQ, LYH and HP carried out the investigation. YY and YR wrote the paper. HZL and LHH checked and finalized the manuscript. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Animal and Human Rights Statement

The study project was submitted to and approved by the Fifth People’s Hospital of Wuxi, Affiliated to Jiangnan University Ethics Committee and the Shanghai Public Health Clinical Center Ethics Committee. The Ethics Committee authorized this study, which was performed with written informed-consent files by patients and was anonymous.


  1. Ammatuna P, Campisi G, Giovannelli L, Giambelluca D, Alaimo C, Mancuso S, Margiotta V (2001) Presence of Epstein-Barr virus, cytomegalovirus and human papillomavirus in normal oral mucosa of HIV-infected and renal transplant patients. Oral Dis 7:34–40PubMedGoogle Scholar
  2. Amornthatree K, Sriplung H, Mitarnun W, Nittayananta W (2012) Effects of long-term use of antiretroviral therapy on the prevalence of oral Epstein-Barr virus. J Oral Pathol Med 41:249–254CrossRefPubMedGoogle Scholar
  3. Balfour HH Jr, Odumade OA, Schmeling DO, Mullan BD, Ed JA, Knight JA, Vezina HE, Thomas W, Hogquist KA (2013) Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis 207:80–88CrossRefPubMedGoogle Scholar
  4. Burnham KE, Cruess DG, Kalichman MO, Grebler T, Cherry C, Kalichman SC (2016) Trauma symptoms, internalized stigma, social support, and sexual risk behavior among HIV-positive gay and bisexual MSM who have sought sex partners online. AIDS Care 28:347–353CrossRefPubMedGoogle Scholar
  5. Cao P, Zhang M, Wang W, Dai Y, Sai B, Sun J, Wang L, Wang F, Li G, Xiang J (2017) Fluorescence in situ hybridization is superior for monitoring Epstein Barr viral load in infectious mononucleosis patients. BMC Infect Dis 17:323CrossRefPubMedPubMedCentralGoogle Scholar
  6. Chakraborty N, Bhattacharyya S, De C, Mukherjee A, Bhattacharya D, Santra S, Sarkar RN, Banerjee D, Guha SK, Datta UK, Chakrabarti S (2010) Incidence of multiple herpesvirus infection in HIV seropositive patients, a big concern for Eastern Indian scenario. Virol J 7:147CrossRefPubMedPubMedCentralGoogle Scholar
  7. Choi SK, Graber CJ (2014) Acute human immunodeficiency virus (HIV) syndrome after nonadherence to antiretroviral therapy in a patient with chronic HIV infection: a case report. Open Forum Infect Dis 1:ofu112CrossRefPubMedPubMedCentralGoogle Scholar
  8. Cohen JI, Fauci AS, Varmus H, Nabel GJ (2011) Epstein-Barr virus: an important vaccine target for cancer prevention. Sci Transl Med 3:107fs107CrossRefGoogle Scholar
  9. Dai SY, Liu JJ, Fan YG, Shan GS, Zhang HB, Li MQ, Ye DQ (2015) Prevalence and factors associated with late HIV diagnosis. J Med Virol 87:970–977CrossRefPubMedGoogle Scholar
  10. de Franca TR, de Albuquerque Tavares Carvalho A, Gomes VB, Gueiros LA, Porter SR, Leao JC (2012) Salivary shedding of Epstein-Barr virus and cytomegalovirus in people infected or not by human immunodeficiency virus 1. Clin Oral Investig 16:659–664CrossRefPubMedGoogle Scholar
  11. de-The G, Day NE, Geser A, Lavoue MF, Ho JH, Simons MJ, Sohier R, Tukei P, Vonka V, Zavadova H (1975) Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study—a review. IARC Sci Publ 11:3–16Google Scholar
  12. Fourcade G, Germi R, Guerber F, Lupo J, Baccard M, Seigneurin A, Semenova T, Morand P, Epaulard O (2017) Evolution of EBV seroprevalence and primary infection age in a French hospital and a city laboratory network, 2000–2016. PLoS One 12:e0175574CrossRefPubMedPubMedCentralGoogle Scholar
  13. Grimes RM, Hardwicke RL, Grimes DE, DeGarmo DS (2016) When to consider acute HIV infection in the differential diagnosis. Nurse Pract 41:1–5CrossRefGoogle Scholar
  14. Guidry JT, Birdwell CE, Scott RS (2017) Epstein-Barr virus in the pathogenesis of oral cancers. Oral Dis. PubMedCrossRefGoogle Scholar
  15. Hanley PJ, Cruz CRY, Savoldo B, Leen AM, Stanojevic M, Khalil M, Decker W, Molldrem JJ, Liu H, Gee AP, Rooney CM, Heslop HE, Dotti G, Brenner MK, Shpall EJ, Bollard CM (2009) Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood 114:1958–1967CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kelly H, Weiss HA, Benavente Y, de Sanjose S, Mayaud P, ART and HPV Review Group (2018) Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis. Lancet HIV 5:e45–e58CrossRefPubMedGoogle Scholar
  17. Liu G, Sharma M, Tan N, Barnabas R (2018) HIV-positive women have higher risk of HPV infection, precancerous lesions, and cervical cancer: a systematic review and meta-analysis. AIDS 32:795–808CrossRefPubMedGoogle Scholar
  18. Mocroft A, Lundgren JD, Sabin ML, Monforte A, Brockmeyer N, Casabona J, Castagna A, Costagliola D, Dabis F, De Wit S, Fatkenheuer G, Furrer H, Johnson AM, Lazanas MK, Leport C, Moreno S, Obel N, Post FA, Reekie J, Reiss P, Sabin C, Skaletz-Rorowski A, Suarez-Lozano I, Torti C, Warszawski J, Zangerle R, Fabre-Colin C, Kjaer J, Chene G, Grarup J, Kirk O (2013) Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE). PLoS Med 10:e1001510CrossRefPubMedPubMedCentralGoogle Scholar
  19. Molina Y, Ramirez-Valles J (2013) HIV/AIDS stigma: measurement and relationships to psycho-behavioral factors in Latino gay/bisexual men and transgender women. AIDS Care 25:1559–1568CrossRefPubMedGoogle Scholar
  20. Moriuchi M, Moriuchi H (2003) Increased susceptibility to HIV-1 of peripheral blood lymphocytes in acute infection with Epstein-Barr virus. J Med Virol 71:343–346CrossRefPubMedGoogle Scholar
  21. Porter DD, Wimberly I, Benyesh-Melnick M (1969) Prevalence of antibodies to EB virus and other herpesviruses. JAMA 208:1675–1679CrossRefPubMedGoogle Scholar
  22. Rao SC, Ashraf I, Mir F, Samiullah S, Ibdah JA, Tahan V (2017) Dual infection with hepatitis B and Epstein-Barr virus presenting with severe jaundice, coagulopathy, and hepatitis B virus chronicity outcome. Am J Case Rep 18:170–172CrossRefPubMedPubMedCentralGoogle Scholar
  23. Scaggiante R, Andreis S, Basso M, Franchin E, Franzetti M, Del Vecchio C, Torti C, Mengoli C, Cruciani M, Sarmati L, Palu G, Parisi SG (2016) Epstein-Barr and cytomegalovirus DNA salivary shedding correlate with long-term plasma HIV RNA detection in HIV-infected men who have sex with men. J Med Virol 88:1211–1221CrossRefPubMedGoogle Scholar
  24. Shen Y, Lu H, Wang Z, Qi T, Wang J (2013) Analysis of the immunologic status of a newly diagnosed HIV positive population in China. BMC Infect Dis 13:429CrossRefPubMedPubMedCentralGoogle Scholar
  25. Shin HR, Shin A, Woo H, Fox K, Walsh N, Lo YR, Wiesen E, Varghese C (2016) Prevention of infection-related cancers in the WHO Western Pacific Region. Jpn J Clin Oncol 46:13–22CrossRefPubMedGoogle Scholar
  26. Sun J, Liu L, Shen J, Chen P, Lu H (2017) Trends in baseline CD4 cell counts and risk factors for late antiretroviral therapy initiation among HIV-positive patients in Shanghai, a retrospective cross-sectional study. BMC Infect Dis 17:285CrossRefPubMedPubMedCentralGoogle Scholar
  27. Vargas-Meneses MV, Massanella M, Ignacio CC, Gianella S (2015) Quantification of HIV RNA and human herpesvirus DNA in seminal plasma. Bio Protoc 5:e1465CrossRefPubMedPubMedCentralGoogle Scholar
  28. Wang L, Ge L, Wang L, Morano JP, Guo W, Khoshnood K, Qin Q, Ding Z, Sun D, Liu X, Luo H, Tillman J, Cui Y (2015) Causes of death among AIDS patients after introduction of free combination antiretroviral therapy (cART) in three Chinese provinces, 2010–2011. PLoS ONE 10:e0139998CrossRefPubMedPubMedCentralGoogle Scholar
  29. WHO (2014) WHO Guidelines Approved by the Guidelines Review Committee. Guidelines on Post-Exposure Prophylaxis for HIV and the Use of Co-Trimoxazole Prophylaxis for HIV-Related Infections Among Adults, Adolescents and Children: Recommendations for a Public Health Approach: December 2014 supplement to the 2013 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. World Health Organization Copyright (c) World Health Organization 2014, GenevaGoogle Scholar
  30. Wu Z, Zhao Y, Ge X, Mao Y, Tang Z, Shi CX, Chen C, Li Y, Qiu X, Nong G, Huang S, Luo S, Wu S, He W, Zhang M, Shen Z, Jin X, Li J, Brookmeyer R, Detels R, Montaner J, Wang Y (2015) Simplified HIV testing and treatment in China: analysis of mortality rates before and after a structural intervention. PLoS Med 12:e1001874CrossRefPubMedPubMedCentralGoogle Scholar
  31. Xiong G, Zhang B, M-Y Huang, Zhou H, Chen LZ, Feng QS, Luo X, Lin HJ, Zeng YX (2014) Epstein-Barr virus (EBV) infection in Chinese children: a retrospective study of age-specific prevalence. PLoS ONE 9:e99857CrossRefPubMedPubMedCentralGoogle Scholar
  32. Yao Y, Luo Y, He Y, Zheng Y, Zhang Q, Zhou H, Zeng S, Chen Z, He B, He M (2013) The effect of a year of highly active antiretroviral therapy on immune reconstruction and cytokines in HIV/AIDS patients. AIDS Res Hum Retrovir 29:691–697CrossRefPubMedGoogle Scholar
  33. Zhang F, Dou Z, Ma Y, Zhang Y, Zhao Y, Zhao D, Zhou S, Bulterys M, Zhu H, Chen RY (2011) Effect of earlier initiation of antiretroviral treatment and increased treatment coverage on HIV-related mortality in China: a national observational cohort study. Lancet Infect Dis 11:516–524CrossRefPubMedGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Center of Clinical Laboratory, The Fifth People’s Hospital of WuxiAffiliated to Jiangnan UniversityWuxiChina
  2. 2.Wuxi Institute of Hepatology, The Fifth People’s Hospital of WuxiAffiliated to Jiangnan UniversityWuxiChina
  3. 3.The International Joint Research Laboratory for Infection and Immunity (China-Germany), The Fifth People’s Hospital of WuxiAffiliated to Jiangnan UniversityWuxiChina
  4. 4.Wuxi Red Ribbon Care Center of China Red Cross, The Fifth People’s Hospital of WuxiAffiliated to Jiangnan UniversityWuxiChina
  5. 5.The International Joint Research Laboratory for Infection and Immunity (China-Germany), Wuxi School of MedicineJiangnan UniversityWuxiChina
  6. 6.Department of Infectious Diseases, Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina

Personalised recommendations