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Could Anti-retroviral Treatment Affects the Profile of Hepatitis B Vaccine Specific Antibody in Vertically HIV-infected Children?

medrxiv(2023)

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Abstract
Paediatric immunisation had been relevant in reducing the widespread of Hepatitis B virus, as an outcome of the induction of hepatitis B surface antigen specific-IgG antibodies (anti-HBs). Studies revealed alteration effects of memory B cells during antiretroviral therapy (ART). We aimed at assessing anti-HBs response profile with respect to the most prominently used ART regimens in children. a cross-sectional study was conducted in 116 participants made up of 72 HIV-exposed and infected children, subdivided into 20 antiretroviral-naïve on one hand and on another hand 52 ARV treated children made up of regimen subgroups, including 8 ABC-3TC-EFV/NVP (ART-R1), 19 ABC-3TC-LPV/r (ART-R2), 21 AZT-3TC-NVP (ART-R3) and 4 AZT-3TC-LPV/r (ART-R4), and 44 HIV-uninfected and unexposed (HUx or control group) children. Participants included in this study were regularly vaccinated children aged between 4 months and 5 years old, born to HIV-infected mothers. An optimized and adapted home-made ELISA and BioELISA® Biohit kit were used to measure specific IgM, IgG and IgG subclasses to HBs in children. As result, this study showed that the rates of vaccine protective response in children treated with ART under regimens R1, R2, R3 and R4 were 25%, 38%, 51% and 75%, respectively. These protective response rates were significantly lower (p<0.0001) in children under R1, R2 and R3 than the control group (92%). When comparing anti-HBs specific IgM and IgG response medians; IgM response levels were similar in both control and ARV treated children, whereas R1 (p=0.0045), R2 (p=0.0016), and R4 (p<0.0001) showed significantly lower IgG level compared to the control group. Anti-HBs IgG subclass profile pattern in the control was IgG3≈IgG1≈IgG4>IgG2. However, IgG3≈IgG1≈IgG4>IgG4 profile pattern was estimated for children submitted to R1, R2 and R4, and the profile pattern of IgG3>IgG1≈IgG4≈IgG2 in those treated with R3 which also showed the most prominent anti-HBs IgG response mean rank level. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Grand Challenge Canada grant (0121-01) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Cameroon National Ethical Committee for research on health sciences I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes * 3TC : Lamivudine ABC : Abacavir Anti-HBc : Antibody to hepatitis B core antigen Anti-HBs : Antibody to hepatitis B surface antigen ART : Antiretroviral therapy ARV : Antiretroviral ATV/r : Atazanavir/ritonavir AZT : Zidovudine EDTA : Ethylene Diamine Tetraacetique Acid EFV : Efavirenz HBcAg : Hepatitis B Core Antigen HBsAg : Hepatitis B Surface Antigen HBV : Hepatitis B Virus HEI : (HIV-Exposed and infected children): HIV-positive children who are born to HIV-infected mother HEI/ARV : (Antiretroviral-naïve HIV-Exposed and infected children): HIV-positive children who are born to HIV-infected mother HEI/ARV : (HIV-Exposed and infected children treated to antiretroviral): HIV-positive children who are born to HIV-infected mother HUx : (HIV-unexposed and uninfected children): control group of children born to HIV negative mothers. LPV/r : Lopinavir/ritonavir NVP : Nevirapine R/ART-R : Specific Antiretroviral therapy Regimen [( R1/ART-R1 : Abacavir-Lamivudine-Efevirenz or Niverapine (ABC-3TC-EFV/NVP), R2/ART-R2 : Abacavir-Lamivudine-Lopinavir/ritonavir (ABC-3TC-LPV/r), R3/ART-R3 : Zidovudine-Lamivudine-Niverapine (AZT-3TC-NVP), R4/ART-R4 : Zidovudine-Lamivudine-Lopinavir/ritonavir (AZT-3TC-LPV/r)]
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