Randomized study of intradermal compared to intramuscular hepatitis B vaccination in HIV-infected children without severe immunosuppression.

HIV infected individuals have poorer response to hepatitis B vaccine (HBV) compared to normal host. Intradermal administration (i.d.) facilitates the exposure of antigen to antigen-presenting cells compared to intramuscular administration (i.m.). HIV-infected children aged 1-18 years with CD4%≥15% or 200 cells/mm(3) who had negative HBs Ag, antiHBs, and antiHBc were randomized to receive 3-dose of HBV via i.d. (2 µg/dose) or i.m. (10 µg/dose) route at months 0, 2, and 6. AntiHBs titers were measured at months 2, 6 and 7 after first HBV. AntiHBs≥10 mIU/mL was considered protective and AntiHBs>100 mIU/mL was considered good response. Participants included 41 in i.d. and 39 in i.m. arms. 64% had completed 3-doses HBV during infancy. The mean (SD) of age, nadir CD4% and current CD4% were 12 (3.3) years, 10.6 (7.9)% and 28 (8.0)% respectively. 91% were on HAART and 84% had undetectable HIV-RNA. Proportion of children with protective antiHBs in i.d. vs. i.m. group were 19.5% vs. 25.6% at month 2, 56.1% vs. 76.9% at month 6, and 90.2% vs. 92.3% at month 7 (NS, all). The geometric mean (95% confidence interval) of antiHBs titer in i.d. vs. i.m. group were 112.5 (34.4-367.6) vs. 141.2 (49.4-404.1) mIU/mL at month 2 (p=0.74), 70.4 (39.8-124.4) vs. 132.1 (79.4-219.8) mIU/mL at month 6 (p=0.10), and 157.0 (103.0-239.3) vs. 458.9 (324.0-647.0) mIU/mL at month 7 (p<0.001). However, only 56.1% of the i.d. arm had good response to HBV compared to 82.1% in the i.m. arm (p=0.01). The predictors for being a good responder to HBV were i.m. administration [OR 4.0, 95%CI 1.4-11.8, p=0.012] and body weight <35 kg at baseline [OR 3.8, 95%CI 1.3-10.8, p=0.013]. No adverse events grade 3/4 occurred. In conclusion, HIV-infected children without severe immune suppression, both i.d. and i.m. routes of HBV resulted in similar rates of protective antibody titers. However, high antibody titers to HBV were more common with i.m.; therefore, i.m. administration is preferred.

The immunogenicity and safety of live attenuated varicella-zoster virus vaccine in human immunodeficiency virus-infected children.

BACKGROUND: The live attenuated varicella vaccine is recommended for HIV-infected children who are not severely immunosuppressed. This study aimed to assess the immunogenicity and safety of varicella vaccination among HIV-infected children who had severe immunosuppression before receiving antiretroviral therapy. METHODS: Sixty HIV-infected children with no history of chickenpox or herpes zoster infection with CD4 T lymphocyte counts ≥ 15% or ≥ 200 cell/mm were enrolled. Two doses of varicella vaccine were administered at the time of enrollment and at 3 months. Varicella zoster virus (VZV) antibody was tested at baseline and 3 months after each dose by the enzyme-linked immunosorbent assay technique. An antibody titer >20 HU/mL was regarded as protective. RESULTS: The median (interquartile range) of age, CD4 nadir, and current CD4 percentage were 11.2 (8.5-12.8) years, 9.5% (3-14), and 28% (22-32), respectively. Fifty-seven children (95%) received antiretroviral therapy for a median of 27 months. Among 34 children (57%) who were VZV seronegative at baseline, 11.8% (95% CI, 3.3%-27.5%) and 79.4% (95% CI, 62.1%-91.3%) were VZV seroconverted after first and second dose of vaccine, respectively. Children who had VZV seroconversion were more likely to have HIV RNA <1.7 copies/mL (92.6% vs. 71.4%, P = 0.18). Among 26 children who were seropositive at baseline, the geometric mean titers were increased from 56.7 to 107.9 and 134.6 unit/mL, respectively. Local and systemic reactions of grade 1 and 2 were reported in 13% and 4% of children, respectively. There was a trend toward better response among children with younger age, high CD4, and viral suppression. CONCLUSIONS: Administration of the 2 doses of varicella vaccine resulted in high seroconversion rates without serious adverse reactions. Varicella vaccination for HIV-infected children should be encouraged.