The Immunogenicity and Safety of Pneumococcal Conjugate Vaccine in Human Immunodeficiency Virus-Infected Thai Children Chareeya Thanee 1 , Chitsanu Pancharoen 1 , Sasithorn Likitnukul 1 , Voravich Luangwedchakarn 3 , Pinklow Umrod 3 , Chayapa Phasomsap 2 , Tanakorn Apornpong 2 , Thongsuai Chuanchareon 2 , Oratai Butterworth 2 , Thanyawee Puthanakit 1,2 1 Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 2 The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), the Thai Red Cross AIDS Research Centre, Bangkok, Thailand; 3 Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Poster P_94 Mailing Address: Chareeya Thanee, MD Division of Infectious Diseases, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand Email: chareeya_thn@hotmail.com The 3rd International Workshop on HIV Pediatrics, Rome, Italy July 2011 The risk of invasive pneumococcal diseases (IPD) is 21 fold greater in HIV-infected children compared to HIV-uninfected children in those < 2 years and 32 fold greater in children 2-4 years of age [1]. The response to PCV is variable depending upon pneumococcal serotype, immunological status and duration of antiretroviral therapy [2-7]. To determine the immunogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV-7) in Thai HIV-infected children compared to HIV-exposed uninfected children. The subjects were enrolled during April to December 2010. The median (IQR) age was 61 months (51-73) and 97 months (67-111) among HIV-exposed uninfected children and HIV-infected children, respectively (p<0.001). Among HIV-infected group, the median (IQR) nadir CD4% was 14% (7-21). Median current CD4% was 30% (25-35), median current CD4 counts was 1079 cell/mm3 (723-1326). Median duration of HAART is 24 months (12-42) and 46 children (82%) had HIV viral load <50 copies/mL. Immunogenicity PCV-7 is highly immunogenic and safe among HIV-infected children treated with HAART. The use of the pneumococcal conjugate vaccine among HIV-infected children is encouraged in order to prevent IPD. Background Objective Material and Methods Study population: children aged 2 months to 9 years of age, HIV-infected (N=59) and HIV-exposed uninfected children (N=30) The exclusion criteria: previous vaccination with pneumococcal vaccine (PCV or PPV), active opportunistic infection, and use of oral steroids/immunosuppressive drugs. Study vaccine: a 7-valent pneumococcal conjugate vaccine, (Prevnar-7), Wyeth Pharmaceutical, NY USA. Each 0.5 ml IM administration. Study procedure: The number of vaccines depended on age and HIV serostatus (Figure 1). PCV serotype-specific IgG antibody was measured at 2 time points (baseline and 28 days after completion of primary vaccine series) using the 3rd generation ELISA according to WHO protocol. Results Conclusion Abstract Background: HIV-infected children have a higher risk of invasive pneumococcal disease (IPD) than uninfected children, despite receiving highly active antiretroviral therapy (HAART). This study was aimed to determine the immunogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV-7) in Thai HIV-infected children compared to HIV-exposed uninfected children. Methods: A prospective study was conducted among children 2 months to 9 years. The number of PCV-7 doses depended upon age and HIV status; 2-6 months of age: 3 doses; 7-23 months of age: 2 doses; HIV-infected child ≥ 24 months: 2 doses and HIV-exposed uninfected child ≥ 24 months: 1 dose. Serotype-specific IgG antibody concentrations were measured at baseline and 28 days after complete primary series of vaccination. Antipneumococcal IgG antibodies of serotype 4, 6B, 9V, 14, 18C, 19F and 23F were performed by 3rd generation enzyme-linked immunosorbent assay method. The primary end point was a proportion of children achieved serotype-specific IgG antibody concentration at cut off level ≥0.35 g/mL. Secondary end points were a 4-fold increase in serotype-specific IgG antibody, rates of adverse events and predictors for seroconversion among HIV-infected children. Results: Fifty-nine HIV-infected and 30 HIV-exposed uninfected children were enrolled. The median (IQR) age was 97 months (67-111) and 61 months (51-73) among HIV-infected and HIV-exposed uninfected children, respectively (p<0.001). Among HIV-infected children, current and nadir CD4 counts were 1079 cell/mm3 and 461 cell/mm3, respectively. Fifty-three children were receiving antiretroviral therapy. The proportion of children who achieved antipneumococcal IgG ≥0.35 g/mL was in the range of 85%-98% in HIV-infected and 83%-100% in HIV-exposed uninfected children depending on serotype. The lowest response was on serotype 6B in both groups. The 4-fold increase in serotype-specific IgG concentrations was similar between HIV-infected and HIV-exposed uninfected group except for serotype 9V (p=0.027). HIV-infected children who had history of AIDS had a lower antibody response in serotype 23F (p=0.025). Seven (12%) HIV-infected children had a grade 3 local reaction with spontaneous recovery after first dose of PCV vaccination. Conclusion: PCV-7 is highly immunogenic and safe among HIV-infected children after receiving HAART. The use of pneumococcal conjugate vaccine among HIV-infected children is encouraged in order to prevent invasive pneumococcal diseases. Acknowledgements The authors appreciate the participation of patients and their families. Study funded by Ratchadaphiseksomphot Endowment Fund, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Pneumococcal vaccines were provided by Disease Control Division, Ministry of Public Health, Bangkok. The 4-fold increase in serotype-specific IgG concentrations was similar between HIV-infected and HIV-exposed uninfected group except for serotype 9V (p=0.027). HIV-infected children who had history of AIDS had a lower antibody response in serotype 23F (p=0.025). Safety References [1] Nunes MC. et al. AIDS 2011;25:453-62. [5] King JC. et al. Pediatrics 1997;99:575-80. [2] Spoulou VI. Et al. Vaccine 2005;23:5289-93. [6] Madhi SA. et al. Pediatr Infect Dis J 2005;24:410-6. [3] Nachman S. et al. Pediatrics 2003;112:66-73. [7] Tarrago D. et al. Clin Diagn Lab Immunol 2005;12:165-70. [4] Abzug MJ. et al. Pediatr Infect Dis J 2006;25:920-9. Thanee C, Pancharoen C, Likitnukul S, Luangwedchakarn V, Umrod P, Phasomsap C, Apornpong T, Chuanchareon T, Butterworth O,Puthanakit T. The Immunogenicity and Safety of Pneumococcal Conjugate Vaccine in Human Immunodeficiency Virus-Infected Thai Children. Vaccine 2011 (in press) Table 1: Adverse reactions after PCV-7 immunization in HIV-infected children comparing to HIV-exposed uninfected children Grading Local reactions Fever Systemic reactions HIV HIV HIV HIV HIV HIV negative positive negative positive negative positive N=30 (%) N=59 (%) N=30 (%) N=59 (%) N=30 (%) N=59 (%) After 1st dose 1 14 (46.67) 18 (30.51) 1 (3.33) 1 (1.69) 6 (20.00) 14 (23.73) 2 3 (10.00) 1 (1.69) 0 (0.00) 0 (0.00) 3 (10.00) 5 (8.47) 3 0 (0.00) 7 (11.86)* 0 (0.00) 0 (0.00) 0 (0.00) 1 (1.69) After 2nd dose** 1 1 (16.67) 15 (25.86) 0 (0.00) 0 (0.00) 3 (50.00) 19 (32.76) 2 0 (0.00) 3 (5.17) 1 (16.67) 1 (1.72) 1 (16.67) 0 (0.00) 3 1 (16.67) 5 (8.62) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) * HIV-infected children had higher grade 3 local reaction compared to HIV-exposed uninfected children (p=0.034). ** Numbers of HIV-exposed uninfected and HIV-infected children that received 2nd dose of vaccination were 6 and 59, respectively. 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