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.

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 <15% and screening CD4 cell percentage <15%; stratum 2, pre-HAART nadir CD4 cell percentage <15% and screening CD4 cell percentage ≥15%; stratum 3, pre-HAART nadir CD4 cell percentage 15% to <25% and screening CD4 cell percentage ≥15%; and stratum 4, pre-HAART nadir CD4 cell percentage ≥25% and screening CD4 cell percentage ≥25%). Hepatitis B virus vaccine booster was given at week 0.

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 <10 mIU/mL did not exceed 10 mIU/mL at any of the subsequent time points, the median concentration in stratum 4 was higher than that in strata 2 and 3 at week 8 (7.2 mIU/mL in stratum 4 vs 2.5 mIU/mL in strata 2 and 3) and week 48 (5.3 mIU/mL in stratum 4 versus 2.5 mIU/mL in strata 2 and 3) but not at week 96 (2.5 mIU/mL in strata 2–4). Stratum 1 is not included because of the small number of subjects in each subgroup. Hepatitis B virus vaccine booster was given at week 0. Ab, anti-HBs.