Background:  Immune reconstitution engendered by HAART is not always associated with full recovery of functional immunity in patients with advanced HIV-disease. We investigated the antibody responses of children on HAART after a standard 2-dose hepatitis A virus vaccine (HAVV) regimen and after a third booster dose.

Methods:  In PACTG 1008 study, 235 HIV-infected children (2 to 21 years old) were enrolled if they had met the indications for and received PCP prophylaxis for >6 months, but had a sustained response to HAART with CD4 >20% for >16 weeks. Children received the standard HAVV immunization regimen, 2 doses 6 months apart, and a third booster dose at 2 years. Anti-HAV antibody were measured at baseline, 8 weeks after the second HAVV, at 2 years, and 8 weeks after the third HAVV. An ELISA titer >20 IU/mL defined a response, but titers >20 and <250 IU/mL were considered low responses.

Results:  Among 149 seronegative children, the median antibody titers after the second immunization was 328 IU/mL. 97% of subjects developed protective antibody, but 44% were low responders. Low responders did not differ significantly from patients with titers >250 IU/mL with respect to age, sex, ethnicity, baseline CD4%, or length of time with CD4>15%. However, low responders had significantly lower CD4% at the second immunization compared with other patients (30% vs 33%, p = 0.04). After 2 years, 104/114 patients (91%) maintained protective titers. Of the 10 patients with titers <20 IU/mL, 2 had never developed a protective response, 7 had titers >20 but <250 after the second HAVV and 1 had titers >250 IU/mL. The data show that low antibody responses after the standard HAVV immunization schedule were significantly associated with accelerated loss of protection (p = 0.001). The median antibody titer before the third dose of vaccine was 98 IU/mL, a 67% loss over 18 months. After the third dose of HAVV 73/75 patients (97%) had protective titers. The median titer was 760 IU/mL and only 20% of subjects had low responses (p = 0.001 and 0.07, respectively, vs second HAVV). Patients who received 3 doses of HAVV did not differ from the other subjects with respect to age, sex, and baseline CD4%. Mean CD4% was similar at the second and third immunizations. There were no grade 3 or 4 adverse events related to HAVV.

Conclusions:  HIV-infected children with evidence of immune reconstitution on HAART showed decreased magnitude and persistence of antibody in response to a standard HAVV regimen despite adequate CD4%. A third dose of HAVV was safe and significantly increased the antibody titers indicating that boosted immunization schedules might be beneficial in these patients.

Keywords: Immunizations; Immune reconstitution; Hepatitis A Virus Vaccine