Immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody

Nattinee Laksananun, Jutarat Praparattanapan, Wilai Kotarathititum, Khuanchai Supparatpinyo, Romanee Chaiwarith, Nattinee Laksananun, Jutarat Praparattanapan, Wilai Kotarathititum, Khuanchai Supparatpinyo, Romanee Chaiwarith

Abstract

Background: Presence of isolated anti-HBc antibody is common in HIV-infected patients in endemic areas and could be caused by prior HBV infection with loss of anti-HBs antibody. The role of vaccination in these patients remains controversial and is based largely on limited and low quality data. We, therefore, conducted this study to determine immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody.

Methods: An open-label, randomized controlled trial was conducted among HIV-infected patients visiting HIV clinic of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand between July and September 2017. Inclusion criteria included ≥ 18 years of age, currently on a stable antiretroviral regimen, CD4+ cell count ≥ 200 cells/mm3, plasma HIV-1 RNA < 20 copies/mL, and isolated anti-HBc antibody. The participants were randomized to receive either 3 standard doses (20 µg at month 0, 1, 6) or 4 standard-doses (20 µg at month 0, 1, 2, 6) of IM HBV vaccination, and were evaluated for anamnestic response at week 4 and vaccine response at week 28.

Results: Of the 97 patients screened, 54 (32 male, mean age of 46 years) were enrolled and 27 were allocated to each of the vaccination groups. Anamnestic response occurred in 25.9% vs. 33.3% in 3-dose group vs. 4-dose group, respectively (p = 0.551). The vaccine response rates at week 28 were 85.2% in 3-dose group vs. 88.9% in 4-dose group (p = 1.000); geometric mean titer of anti-HBs antibody at week 28 was 63.8 and 209.8 mIU/mL in 3-dose group and 4-dose group, respectively (p = 0.030). No adverse events were reported.

Conclusions: An anamnestic response occurred in one-third of Thai HIV-infected patients with isolated anti-HBc antibody who received one dose of HBV vaccination; however, the majority were still unprotected. The use of either 3 or 4 standard-doses of vaccination was highly effective and should be recommended in all HIV-infected individuals with isolated anti-HBc antibody. Trial registration ClinicalTrials.gov; NCT03212911. Registered 11 July 2019, https://ichgcp.net/clinical-trials-registry/NCT03212911.

Keywords: Anamnestic response; HBV vaccination; HIV-infected adults; Immunological response; Isolated anti-HBc antibody.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Consort diagram of study participants
Fig. 2
Fig. 2
Percentages of responders (anti-HBs ≥ 10 mIU/mL) by vaccination regimen
Fig. 3
Fig. 3
Percentages of high-level responders (anti-HBs ≥ 100 mIU/mL) by vaccination regimen
Fig. 4
Fig. 4
Geometric mean titer (GMT) of anti-HBs by vaccination regimen

References

    1. Salmon-Ceron D, Lewden C, Morlat P, Bevilacqua S, Jougla E, Bonnet F, et al. Liver disease as a major cause of death among HIV infected patients: role of hepatitis C and B viruses and alcohol. J Hepatol. 2005;42:799–805. doi: 10.1016/j.jhep.2005.01.022.
    1. Thio CL, Seaberg EC, Skolasky R, Jr, Phair J, Visscher B, Munoz A, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the multicenter cohort study (MACS) Lancet. 2002;360:1921–1926. doi: 10.1016/S0140-6736(02)11913-1.
    1. Kim HN, Harrington RD, Crane HM, Dhanireddy S, Dellit TH, Spach DH. Hepatitis B vaccination in HIV-infected adults: current evidence, recommendations and practical considerations. Int J STD AIDS. 2009;20:595–600. doi: 10.1258/ijsa.2009.009126.
    1. Kaplan JE, Benson C, Holmes KK, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58:1–207.
    1. Fuster F, Vargas JI, Jensen D, Sarmiento V, Acuna P, Peirano F, et al. CD4/CD8 ratio as a predictor of the response to HBV vaccination in HIV-positive patients: a prospective cohort study. Vaccine. 2016;34:1889–1895. doi: 10.1016/j.vaccine.2016.02.055.
    1. Landrum ML, Huppler Hullsiek K, Ganesan A, Weintrob AC, Crum-Cianflone NF, Barthel RV, et al. Hepatitis B vaccine responses in a large U.S. military cohort of HIV-infected individuals: another benefit of HAART in those with preserved CD4 count. Vaccine. 2009;27:4731–4738. doi: 10.1016/j.vaccine.2009.04.016.
    1. Pettit NN, De Pestel DD, Malani PN, Riddell JT. Factors associated with seroconversion after standard dose hepatitis B vaccination and high-dose revaccination among HIV-infected patients. HIV Clin Trials. 2010;11:332–339. doi: 10.1310/hct1105-332.
    1. Potsch DV, Camacho LA, Tuboi S, Villar LM, Miguel JC, Ginuino C, et al. Vaccination against hepatitis B with 4-double doses increases response rates and antibodies titers in HIV-infected adults. Vaccine. 2012;30:5973–5977. doi: 10.1016/j.vaccine.2012.07.028.
    1. Gandhi RT, Wurcel A, Lee H, McGovern B, Shopis J, Geary M, et al. Response to hepatitis B vaccine in HIV-1-positive subjects who test positive for isolated antibody to hepatitis B core antigen: implications for hepatitis B vaccine strategies. J Infect Dis. 2005;191:1435–1441. doi: 10.1086/429302.
    1. Pasricha N, Datta U, Chawla Y, Singh S, Arora SK, Sud A, et al. Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine. BMC Infect Dis. 2006;6:65. doi: 10.1186/1471-2334-6-65.
    1. Collier AC, Corey L, Murphy VL, Handsfield HH. Antibody to human immunodeficiency virus (HIV) and suboptimal response to hepatitis B vaccination. Ann Intern Med. 1988;109:101–105. doi: 10.7326/0003-4819-109-2-101.
    1. Fonseca MO, Pang LW, de Paula Cavalheiro N, Barone AA, Heloisa Lopes M. Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose. Vaccine. 2005;23:2902–2908. doi: 10.1016/j.vaccine.2004.11.057.
    1. Launay O, van der Vliet D, Rosenberg AR, Michel ML, Piroth L, Rey D, et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA. 2011;305:1432–1440. doi: 10.1001/jama.2011.351.
    1. Rey D, Krantz V, Partisani M, Schmitt MP, Meyer P, Libbrecht E, et al. Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load. Vaccine. 2000;18:1161–1165. doi: 10.1016/S0264-410X(99)00389-8.
    1. Chaiklang K, Wipasa J, Chaiwarith R, Praparattanapan J, Supparatpinyo K. Comparison of immunogenicity and safety of four doses and four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: a randomized, controlled trial. PLoS ONE. 2013;8:e80409. doi: 10.1371/journal.pone.0080409.
    1. Filippini P, Coppola N, Pisapia R, Scolastico C, Marrocco C, Zaccariello A, et al. Impact of occult hepatitis B virus infection in HIV patients naive for antiretroviral therapy. AIDS. 2006;20:1253–1260. doi: 10.1097/01.aids.0000232232.41877.2a.
    1. Shire NJ, Rouster SD, Rajicic N, Sherman KE. Occult hepatitis B in HIV-infected patients. J Acquir Immune Defic Syndr. 2004;36:869–875. doi: 10.1097/00126334-200407010-00015.
    1. Tsui JI, French AL, Seaberg EC, Augenbraun M, Nowicki M, Peters M, et al. Prevalence and long-term effects of occult hepatitis B virus infection in HIV-infected women. Clin Infect Dis. 2007;45:736–740. doi: 10.1086/520989.
    1. Azadmanesh K, Mohraz M, Aghakhani A, Edalat R, Jam S, Eslamifar A, et al. Occult hepatitis B virus infection in HIV-infected patients with isolated hepatitis B core antibody. Intervirology. 2008;51:270–274. doi: 10.1159/000160217.
    1. Karaosmanoglu HK, Aydin OA, Nazlican O. Isolated anti-HBc among HIV-infected patients in Istanbul, Turkey. HIV Clin Trials. 2013;14:17–20. doi: 10.1310/hct1401-17.
    1. Neau D, Winnock M, Jouvencel AC, Faure M, Castera L, Legrand E, et al. Occult hepatitis B virus infection in HIV-infected patients with isolated antibodies to hepatitis B core antigen: Aquitaine cohort, 2002–2003. Clin Infect Dis. 2005;40:750–753. doi: 10.1086/427882.
    1. Santos EA, Yoshida CF, Rolla VC, Mendes JM, Vieira IF, Arabe J, et al. Frequent occult hepatitis B virus infection in patients infected with human immunodeficiency virus type 1. Eur J Clin Microbiol Infect Dis. 2003;22:92–98.
    1. Witt MD, Lewis RJ, Rieg G, Seaberg EC, Rinaldo CR, Thio CL. Predictors of the isolated hepatitis B core antibody pattern in HIV-infected and -uninfected men in the multicenter AIDS cohort study. Clin Infect Dis. 2013;56:606–612. doi: 10.1093/cid/cis908.
    1. Waite J, Gilson RJ, Weller IV, Lacey CJ, Hambling MH, Hawkins A, et al. Hepatitis B virus reactivation or reinfection associated with HIV-1 infection. AIDS. 1988;2:443–448. doi: 10.1097/00002030-198812000-00006.
    1. Pei R, Grund S, Verheyen J, Esser S, Chen X, Lu M. Spontaneous reactivation of hepatitis B virus replication in an HIV coinfected patient with isolated anti-Hepatitis B core antibodies. Virol J. 2014;11:9. doi: 10.1186/1743-422X-11-9.
    1. Bani-Sadr F, Maillard A, Ponscarme D, Scieux C, Molina JM. Reactivation of HBV replication in HIV-HBV infected patients. Am J Med. 2003;114:768–769. doi: 10.1016/S0002-9343(03)00156-6.
    1. Chakvetadze C, Bani-Sadr F, Le Pendeven C, Lescure FX, Fontaine C, Galperine T, et al. Serologic response to hepatitis B vaccination in HIV-Infected patients with isolated positivity for antibodies to hepatitis B core antigen. Clin Infect Dis. 2010;50:1184–1186. doi: 10.1086/651422.
    1. Kaech C, Pache I, Burgisser P, Elzi L, Darling KE, Cavassini M. Immune response to hepatitis B vaccination in HIV-positive adults with isolated antibodies to HBV core antigen. J Infect. 2012;65:157–164. doi: 10.1016/j.jinf.2012.03.009.
    1. Jongjirawisan Y, Ungulkraiwit P, Sungkanuparph S. Isolated antibody to hepatitis B core antigen in HIV-1 infected patients and a pilot study of vaccination to determine the anamnestic response. J Med Assoc Thai. 2006;89:2028–2034.
    1. Ural O, Findik D. The response of isolated anti-HBc positive subjects to recombinant hepatitis B vaccine. J Infect. 2001;43:187–190. doi: 10.1053/jinf.2001.0878.
    1. Rockstroh JK, Bhagani S, Benhamou Y, Bruno R, Mauss S, Peters L, et al. European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV-infected adults. HIV Med. 2008;9:82–88. doi: 10.1111/j.1468-1293.2007.00535.x.
    1. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. . Accessed 7 Aug 2017.
    1. Morsica G, Bagaglio S, Spagnuolo V, Castagna A, Di Serio C, Galli A, et al. Immune response to hepatitis B vaccination in HIV-positive individuals with isolated antibodies against hepatitis B core antigen: results of a prospective Italian study. PLoS ONE. 2017;12:e0184128. doi: 10.1371/journal.pone.0184128.
    1. Piroth L, Launay O, Michel ML, Bourredjem A, Miailhes P, Ajana F, et al. Vaccination against hepatitis B virus (HBV) in HIV-1-infected patients with isolated anti-HBV core antibody: the ANRS HB EP03 CISOVAC prospective study. J Infect Dis. 2016;213:1735–1742. doi: 10.1093/infdis/jiw011.
    1. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. 2017. . Accessed 30 Mar 2018.
    1. Raimondo G, Pollicino T, Cacciola I, Squadrito G. Occult hepatitis B virus infection. J Hepatol. 2007;46:160–170. doi: 10.1016/j.jhep.2006.10.007.
    1. Carne C, Weller I, Waite J, Briggs M, Pearce F, Adler M, et al. Impaired responsiveness of homosexual men with HIV antibodies to plasma derived hepatitis B vaccine. Br Med J (Clin Res Ed) 1987;294:866–868. doi: 10.1136/bmj.294.6576.866.
    1. Wong EK, Bodsworth NJ, Slade MA, Mulhall BP, Donovan B. Response to hepatitis B vaccination in a primary care setting: influence of HIV infection, CD4+ lymphocyte count and vaccination schedule. Int J STD AIDS. 1996;7:490–494. doi: 10.1258/0956462961918563.
    1. Fisman DN, Agrawal D, Leder K. Effect of age on immunologic response to recombinant hepatitis B vaccine: a meta-analysis. Clin Infect Dis. 2002;35:1368–1375. doi: 10.1086/344271.
    1. Hamborsky J, Kroger A, Wolfe S, Control CFD, Prevention . Epidemiology and prevention of vaccine-preventable diseases. Atlanta: US Department of Health & Human Services, Centers for Disease Control and Prevention; 2015.
    1. Yang S, Tian G, Cui Y, Ding C, Deng M, Yu C, et al. Factors influencing immunologic response to hepatitis B vaccine in adults. Sci Rep. 2016;6:27251. doi: 10.1038/srep27251.
    1. McKinnon LR, Kimani M, Wachihi C, Nagelkerke NJ, Muriuki FK, Kariri A, et al. Effect of baseline HIV disease parameters on CD4+ T cell recovery after antiretroviral therapy initiation in Kenyan women. PLoS ONE. 2010;5:e11434. doi: 10.1371/journal.pone.0011434.
    1. Negredo E, Massanella M, Puig J, Pérez-Alvarez N, Gallego-Escuredo JM, Villarroya J, et al. Nadir CD4 T cell count as predictor and high CD4 T cell intrinsic apoptosis as final mechanism of poor CD4 T cell recovery in virologically suppressed HIV-infected patients: clinical implications. Clin Infect Dis. 2010;50:1300–1308. doi: 10.1086/651689.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner