Protection against flu but not HBV in vaccinated perinatally HIV-infected children

Children perinatally infected with HIV usually had protective levels of antibodies against influenza after three or more vaccinations. But completing a hepatitis B virus (HBV) vaccination schedule usually did not yield protective levels of antibodies against HBV.

B-cell compartment defects in perinatally infected children can thwart responses to standard vaccines, noted University of Texas investigators who conducted this study.

Poor responses to these vaccines and less durable immunity have led to proposals for booster immunisations, modified regimens, modified immunogens, and other revamped vaccination strategies. But now, the Texas team observed, many perinatally infected children have responded well to antiretroviral therapy for several years and have a good immunologic status. Some argue that these children are essentially normal immunologically and that they should follow standard paediatric immunisation schedules.

The University of Texas researchers conducted this study to see if immune responses to influenza and HBV vaccination in perinatally infected children with well-controlled HIV were equivalent to responses in HIV negative adults. They picked influenza and HBV vaccinations because the two have distinct immunisation schedules. All children had received three or more influenza shots and a complete series of HBV immunisations. All had taken antiretroviral therapy for at least 6 months. The researchers selected significantly older HIV negative adults as a rigorous set of controls for immunologic memory. They measured plasma antibodies to influenza (H1N1 and H3N2) and HBV by haemagglutination inhibition and ELISA.

The 21 youngsters with HIV had a median age of 15.2 years, compared with 42.0 in the 11 adult controls. Eleven children with HIV (52%) were girls, 14 (67%) had a viral load below 400 copies, and 7 had a viral load above 400 copies. CD4 percent in the HIV group averaged 29.8%. Only 3 children had started ART within the first year after HIV diagnosis. For the youngsters with HIV, median time elapsed between the last two HBV vaccinations was 10.1 years, and between the last two influenza vaccinations 0.6 year. Vaccine-specific antibody titers to H1N1 and H3N2 did not differ substantially between the youngsters with HIV and HIV negative controls, regardless of HIV load in the children. Antibody titers to HBV were significantly lower in children with HIV than in HIV negative controls, and the titers did not differ between children with a viral load above versus below 400 copies.

Defining protective titers against H1N1 and H3N2 as >1.4, the investigators found no significant difference in proportions protected between either HIV group (above or below 400 HIV RNA copies) and the HIV negative controls. Defining protective titers against HBV as above 2.1, they recorded protective titers in 14.3% of the sub-400-copy HIV group and 28.6% of the 400-plus-copy HIV group, compared with 66.7% of HIV negative controls (p < 0.009 for both comparisons).

The University of Texas team proposed that “the persistence of protective levels of neutralising antibodies to influenza but not HBV in this population may be the consequence of repeated influenza vaccinations.” If that explains the difference between protection against influenza and HBV, they suggested, it could stress “the potential efficacy of providing structurally different [antigen] motifs in an intermittent way to assure a long-lasting immune response in infected children.”