title: Immunogenicity and safety of two doses of catch-up immunization with Haemophilus influenzae type b conjugate vaccine in Indian children living with HIV.
abstract: BACKGROUND
  Children living with HIV are at increased risk of disease from Haemophilus influenzae type b (Hib). Data are limited on the immunogenicity of a two-dose, catch-up schedule for Hib conjugate vaccine (HibCV) among HIV-infected children accessing antiretroviral therapy (ART) late.
  
  
  OBJECTIVE
  The objectives of the study were to: (1) evaluate baseline immunity to Hib and the immunogenicity and safety of two doses of HibCV among HIV-infected Indian children; and (2) document the threshold antibody level required to prevent Hib colonization among HIV-infected children following immunization.
  
  
  METHODS
  We conducted a prospective cohort study among HIV-infected children 2-15 years of age and HIV-uninfected children 2-5 years of age. HIV-infected children received two doses of HibCV and uninfected children received one. Serum anti-Hib PRP IgG antibodies were measured at baseline and two months after immunization in the HIV-infected children. Nasopharyngeal (NP) swabs were collected at baseline and follow-up.
  
  
  RESULTS
  125 HIV-infected and 44 uninfected children participated. 40% of HIV-infected children were receiving ART and 26% had a viral load >100,000 copies/mL. The geometric mean concentration of serum anti-Hib PRP antibody increased from 0.25 μg/mL at baseline to 2.65 μg/mL after two doses of HibCV, representing a 10.6-fold increase (p<0.0001). 76% percent of HIV-infected children mounted an immune response. Moderate or severe immune suppression, trimethoprim/sulfamethoxazole prophylaxis, and lower baseline antibody levels were associated with lower post-vaccine serum anti-Hib PRP IgG antibodies. A serum anti-Hib PRP IgG antibody level ≥ 3.3 μg/mL was protective against Hib NP colonization. There were no differences in adverse events between HIV-infected and uninfected children.
  
  
  CONCLUSIONS
  Including a catch-up immunization schedule for older HIV infected children in countries introducing Hib vaccines is important. Older HIV-infected children with delayed access to ART and without suppressed viral loads mounted an adequate immune response following two doses of HibCV.
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology (IIT) - Kharagpur, India.
authors.forename: Bikas K
authors.initials: BK
authors.lastname: Arya
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology (IIT) - Kharagpur, India. Electronic address: sangeeta@smst.iitkgp.ernet.in.
authors.forename: Sangeeta Das
authors.initials: SD
authors.lastname: Bhattacharya
authors.affiliation: International Vaccine Access Center and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Catherine G
authors.initials: CG
authors.lastname: Sutcliffe
authors.affiliation: National HIV Reference Laboratory/Division of Virology, National Institute of Cholera and Enteric Diseases (NICED)/Indian Council of Medical Research (ICMR)-Kolkata, India.
authors.forename: Malay K
authors.initials: MK
authors.lastname: Saha
authors.affiliation: Department of Pediatrics, Midnapore Medical College and Hospital-Midnapore, India.
authors.forename: Subhasish
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases (NICED)/Indian Council of Medical Research (ICMR)-Kolkata, India.
authors.forename: Swapan Kumar
authors.initials: SK
authors.lastname: Niyogi
authors.affiliation: International Vaccine Access Center and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Moss
authors.affiliation: Division of Epidemiology, National Institute of Cholera and Enteric Diseases (NICED)/Indian Council of Medical Research (ICMR)-Kolkata, India.
authors.forename: Samiran
authors.initials: S
authors.lastname: Panda
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology (IIT) - Kharagpur, India.
authors.forename: Ranjan Saurav
authors.initials: RS
authors.lastname: Das
authors.affiliation: National HIV Reference Laboratory/Division of Virology, National Institute of Cholera and Enteric Diseases (NICED)/Indian Council of Medical Research (ICMR)-Kolkata, India.
authors.forename: Mausom
authors.initials: M
authors.lastname: Mallick
authors.affiliation: Division of Bacteriology, National Institute of Cholera and Enteric Diseases (NICED)/Indian Council of Medical Research (ICMR)-Kolkata, India.
authors.forename: Sutapa
authors.initials: S
authors.lastname: Mandal
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000097:blood; D016667:Bacterial Capsules / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D019741:Haemophilus influenzae type b; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007194:India; D007223:Infant; D008297:Male; D011446:Prospective Studies; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D007074:Immunoglobulin G; D018074:Vaccines, Conjugate
keywords: Anti-Hib PRP IgG; Conjugate vaccines; HIV; Haemophilus influenzae type b; Immune response; Nasopharyngeal carriage