Accepted Manuscript Response to Hepatitis B Virus vaccine in young adults with perinatally acquired HIV infection Dr Manish Sadarangani, Herman Tam, Susan McDonald, Sarah Fidler, Caroline Foster PII:
S0163-4453(15)00198-X
DOI:
10.1016/j.jinf.2015.06.003
Reference:
YJINF 3555
To appear in:
Journal of Infection
Received Date: 26 May 2015 Revised Date:
1 June 2015
Accepted Date: 3 June 2015
Please cite this article as: Sadarangani M, Tam H, McDonald S, Fidler S, Foster C, Response to Hepatitis B Virus vaccine in young adults with perinatally acquired HIV infection, Journal of Infection (2015), doi: 10.1016/j.jinf.2015.06.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Response to Hepatitis B Virus vaccine in young adults with perinatally acquired HIV infection
RI PT
Manish Sadarangania*, Herman Tamb, Susan McDonaldb, Sarah Fidlerb and Caroline Fosterb
Authors’ Affiliations a
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and NIHR
Imperial College Healthcare NHS Trust, London, UK
*Author for correspondence: Dr Manish Sadarangani
M AN U
b
SC
Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford, UK
9DU.
TE D
Department of Paediatrics, University of Oxford, Level 2, Children’s Hospital, Oxford OX3
Telephone: +44 (0)1865 226953
EP
Fax: +44 (0)1865 234235
AC C
Email: [email protected]
Running title: HBV vaccination in HIV infected young adults
1
ACCEPTED MANUSCRIPT Dear Editor, We read with interest the article by Rowley et al. (1) in this journal, in which they described the determinants of serological response to booster vaccination with hepatitis B virus vaccine in HIV-infected non-responders. We now describe data to complement their study, in which
RI PT
we investigated the influence of vaccine dosing interval and other immunological determinants of response to the primary series of HBV vaccine in HIV-infected adolescents
SC
and young adults.
HBV infection is a major public health problem worldwide, despite the availability of an
M AN U
effective vaccine. Individuals with HIV are at greater risk of acquiring HBV and HIV/HBV co-infection has worse outcomes than HBV mono-infection (2). HBV vaccination is not currently included in the routine UK childhood immunisation schedule. The 2013 British HIV Association (BHIVA) guidelines recommend HBV vaccination of all HIV-infected
TE D
individuals with 4 doses of double-dose vaccine (40mcg per dose) at 0, 1, 2 and 6 months with a check of the antibody level 4-8 weeks after the 4th dose (3). A successful vaccine response is indicated by an HBV surface Ag-specific antibody level >10 IU/L, and a level
EP
>100 IU/L is considered ideal (4). Previous recommendations (5) advocated either a 3-dose
AC C
schedule at 0, 1 and 6 months or a 4-dose schedule at 0, 1, 2, 12 months using a standard dose (20mcg per dose). Successfully achieving these specific dosing intervals requires optimal attendance, and is a challenge for adolescents and young adults where clinic attendance maybe less regular than for younger children or older adults (6). Pragmatic management of such erratic attenders has been to offer opportunistic vaccination at irregular intervals; however effects on vaccine response are unknown. Immunogenicity of HBV vaccines in HIV-positive individuals is reduced compared to HIV-negative (7). Previous studies have 2
ACCEPTED MANUSCRIPT demonstrated that CD4 cell count, CD4 nadir and plasma HIV viral load have a significant effect on response to vaccination (5). We demonstrated the impact of erratic dosing of 3 HBV vaccination doses and other immunological parameters on ultimate anti-HBs antibody levels
RI PT
post vaccination.
Records of young adults with perinatally-acquired HIV at St Mary’s Hospital, London were reviewed in August 2013 to identify administration of HBV vaccine and measurement of
SC
anti-HBs antibody level. There were a total of 70 patients in the database, and 36 were excluded: 12 had not received hepatitis B vaccine; 6 had received 10 IU/L, which is almost identical to the response found in a
AC C
randomised controlled trial using 3 doses of 20mcg at 0, 1, 6 months in HIV infected adults (8). The main limitation of this study was the relatively small size of the patient cohort. These data suggest that a pragmatic opportunistic approach can be adopted when administering HBV vaccination in this setting, where it is difficult to ensure regular clinic attendance, as a similar response appears to be elicited with variable dosing intervals. Further studies are required to confirm if this will also be true using this currently recommended regimen of 4 doses of 40mcg over 6 months. 4
ACCEPTED MANUSCRIPT
In our population, CD4 count at vaccine initiation did not influence post-vaccination antibody level. Although almost 50% of the cohort had a CD4 count
S0163-4453(15)00198-X
DOI:
10.1016/j.jinf.2015.06.003
Reference:
YJINF 3555
To appear in:
Journal of Infection
Received Date: 26 May 2015 Revised Date:
1 June 2015
Accepted Date: 3 June 2015
Please cite this article as: Sadarangani M, Tam H, McDonald S, Fidler S, Foster C, Response to Hepatitis B Virus vaccine in young adults with perinatally acquired HIV infection, Journal of Infection (2015), doi: 10.1016/j.jinf.2015.06.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Response to Hepatitis B Virus vaccine in young adults with perinatally acquired HIV infection
RI PT
Manish Sadarangania*, Herman Tamb, Susan McDonaldb, Sarah Fidlerb and Caroline Fosterb
Authors’ Affiliations a
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and NIHR
Imperial College Healthcare NHS Trust, London, UK
*Author for correspondence: Dr Manish Sadarangani
M AN U
b
SC
Biomedical Research Centre, Oxford University Hospitals NHS Trust, Oxford, UK
9DU.
TE D
Department of Paediatrics, University of Oxford, Level 2, Children’s Hospital, Oxford OX3
Telephone: +44 (0)1865 226953
EP
Fax: +44 (0)1865 234235
AC C
Email: [email protected]
Running title: HBV vaccination in HIV infected young adults
1
ACCEPTED MANUSCRIPT Dear Editor, We read with interest the article by Rowley et al. (1) in this journal, in which they described the determinants of serological response to booster vaccination with hepatitis B virus vaccine in HIV-infected non-responders. We now describe data to complement their study, in which
RI PT
we investigated the influence of vaccine dosing interval and other immunological determinants of response to the primary series of HBV vaccine in HIV-infected adolescents
SC
and young adults.
HBV infection is a major public health problem worldwide, despite the availability of an
M AN U
effective vaccine. Individuals with HIV are at greater risk of acquiring HBV and HIV/HBV co-infection has worse outcomes than HBV mono-infection (2). HBV vaccination is not currently included in the routine UK childhood immunisation schedule. The 2013 British HIV Association (BHIVA) guidelines recommend HBV vaccination of all HIV-infected
TE D
individuals with 4 doses of double-dose vaccine (40mcg per dose) at 0, 1, 2 and 6 months with a check of the antibody level 4-8 weeks after the 4th dose (3). A successful vaccine response is indicated by an HBV surface Ag-specific antibody level >10 IU/L, and a level
EP
>100 IU/L is considered ideal (4). Previous recommendations (5) advocated either a 3-dose
AC C
schedule at 0, 1 and 6 months or a 4-dose schedule at 0, 1, 2, 12 months using a standard dose (20mcg per dose). Successfully achieving these specific dosing intervals requires optimal attendance, and is a challenge for adolescents and young adults where clinic attendance maybe less regular than for younger children or older adults (6). Pragmatic management of such erratic attenders has been to offer opportunistic vaccination at irregular intervals; however effects on vaccine response are unknown. Immunogenicity of HBV vaccines in HIV-positive individuals is reduced compared to HIV-negative (7). Previous studies have 2
ACCEPTED MANUSCRIPT demonstrated that CD4 cell count, CD4 nadir and plasma HIV viral load have a significant effect on response to vaccination (5). We demonstrated the impact of erratic dosing of 3 HBV vaccination doses and other immunological parameters on ultimate anti-HBs antibody levels
RI PT
post vaccination.
Records of young adults with perinatally-acquired HIV at St Mary’s Hospital, London were reviewed in August 2013 to identify administration of HBV vaccine and measurement of
SC
anti-HBs antibody level. There were a total of 70 patients in the database, and 36 were excluded: 12 had not received hepatitis B vaccine; 6 had received 10 IU/L, which is almost identical to the response found in a
AC C
randomised controlled trial using 3 doses of 20mcg at 0, 1, 6 months in HIV infected adults (8). The main limitation of this study was the relatively small size of the patient cohort. These data suggest that a pragmatic opportunistic approach can be adopted when administering HBV vaccination in this setting, where it is difficult to ensure regular clinic attendance, as a similar response appears to be elicited with variable dosing intervals. Further studies are required to confirm if this will also be true using this currently recommended regimen of 4 doses of 40mcg over 6 months. 4
ACCEPTED MANUSCRIPT
In our population, CD4 count at vaccine initiation did not influence post-vaccination antibody level. Although almost 50% of the cohort had a CD4 count
