Immunogenicity and immunologic memory after hepatitis B virus booster vaccination in HIV-infected children receiving highly active antiretroviral therapy

Abstract

Background: Hepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)-infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated.

Methods: HIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received 3 doses of HBV vaccine were given an HBV vaccine booster. Concentrations of antibody to hepatitis B surface antigen (anti-HBs) were determined before vaccination and at weeks 8, 48, and 96. A subset of subjects was administered a subsequent dose, and anti-HBs was measured before and 1 and 4 weeks later.

Results: At entry, 24% of 204 subjects were seropositive. Vaccine response occurred in 46% on the basis of seropositivity 8 weeks after vaccination and in 37% on the basis of a 4-fold rise in antibody concentration. Of 69 subjects given another vaccination 4-5 years later, immunologic memory was exhibited by 45% on the basis of seropositivity 1 week after vaccination and by 29% on the basis of a 4-fold rise in antibody concentration at 1 week. Predictors of response and memory included higher nadir and current CD4 cell percentage, higher CD19 cell percentage, and undetectable HIV load.

Conclusions: HIV-infected children frequently lack protective levels of anti-HBs after previous HBV vaccination, and a significant proportion of them do not respond to booster vaccination or demonstrate memory despite receiving HAART, leaving this population insufficiently protected from infection with HBV.

Trial registration: ClinicalTrials.gov NCT00013871.

Conflict of interest statement

Potential conflicts of interest: M.J.L. has received research funding from GlaxoSmithKline Pharmaceuticals (herpes simplex virus vaccine and human papillomavirus vaccine); research funding, intellectual property rights, and consultant fees from Merck & Co; and consultant fees from MedImmune and Astellas Pharmaceuticals. S.A.N. has been a consultant for Medimmune, Merck & Co, and Sanofi Pasteur. S.I.P. has served on the vaccine advisory boards of GlaxoSmithKline Pharmaceuticals (pneumococcal and meningococcal vaccine), Wyeth Pharmaceuticals (pneumococcal vaccine), and Sanofi Pasteur (meningococcal, tetanus, diphtheria, pertussis, poliovirus, and Haemophilus influenzae B vaccine) and has received research funding from Wyeth Pharmaceuticals and Sanofi Pasteur. W.B. has received research funding from GlaxoSmithKline Pharmaceuticals (fosamprenavir). All other authors report no potential conflicts.

Figures

Figure 1

Proportion of P1024 subjects with protective concentrations (≥10 mIU/mL) of antibody to hepatitis B surface antigen (anti-HBs). Percentages are depicted at each P1024 study visit, for all subjects and by immune stratum (stratum 1, pre–highly active antiretroviral therapy [HAART] nadir CD4 cell percentage

Figure 2

Proportion of P1024 subjects with protective concentrations (≥10 mIU/mL) of antibody to hepatitis B surface antigen (anti-HBs) as a function of plasma human immunodeficiency virus (HIV) load at study entry. Differences among HIV load groups were present at weeks 8, 48, and 96 (P ≤ .03, Fisher exact test). Pairwise comparisons demonstrated significant differences at each of these time points (P ≤ .03) between subjects with an HIV load ≤400 copies/mL versus >5000 copies/mL but not between subjects with an HIV load ≤400 copies/mL versus 401–5000 copies/mL or between subjects with an HIV load 401–5000 copies/mL versus >5000 copies/mL. Hepatitis B virus vaccine booster was given at week 0.

Figure 3

Median concentrations of antibody to hepatitis B surface antigen (anti-HBs) in P1024. Subjects are divided according to the presence or absence of protective antibody concentrations (≥10 mIU/mL) at entry and immune stratum (see figure 1). Higher median antibody concentrations at weeks 8, 48, and 96 were seen in subjects with baseline antibody concentrations ≥10 mIU/mL, and among these subjects the median concentration in stratum 4 was higher than that in strata 2 and 3 at weeks 8, 48, and 96. Although median antibody concentrations among subjects with baseline antibody concentrations